RNA

Last updated

A hairpin loop from a pre-mRNA. Highlighted are the nucleobases (green) and the ribose-phosphate backbone (blue). This is a single strand of RNA that folds back upon itself. Pre-mRNA-1ysv-tubes.png
A hairpin loop from a pre-mRNA. Highlighted are the nucleobases (green) and the ribose-phosphate backbone (blue). This is a single strand of RNA that folds back upon itself.

Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid (DNA) are nucleic acids. Along with lipids, proteins, and carbohydrates, nucleic acids constitute one of the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA, RNA is found in nature as a single strand folded onto itself, rather than a paired double strand. Cellular organisms use messenger RNA (mRNA) to convey genetic information (using the nitrogenous bases of guanine, uracil, adenine, and cytosine, denoted by the letters G, U, A, and C) that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

Contents

Some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these active processes is protein synthesis, a universal function in which RNA molecules direct the synthesis of proteins on ribosomes. This process uses transfer RNA (tRNA) molecules to deliver amino acids to the ribosome, where ribosomal RNA (rRNA) then links amino acids together to form coded proteins.

Comparison with DNA

Three-dimensional representation of the 50S ribosomal subunit. Ribosomal RNA is in ochre, proteins in blue. The active site is a small segment of rRNA, indicated in red. 50S-subunit of the ribosome 3CC2.png
Three-dimensional representation of the 50S ribosomal subunit. Ribosomal RNA is in ochre, proteins in blue. The active site is a small segment of rRNA, indicated in red.

The chemical structure of RNA is very similar to that of DNA, but differs in three primary ways:

Like DNA, most biologically active RNAs, including mRNA, tRNA, rRNA, snRNAs, and other non-coding RNAs, contain self-complementary sequences that allow parts of the RNA to fold [5] and pair with itself to form double helices. Analysis of these RNAs has revealed that they are highly structured. Unlike DNA, their structures do not consist of long double helices, but rather collections of short helices packed together into structures akin to proteins.

In this fashion, RNAs can achieve chemical catalysis (like enzymes). [6] For instance, determination of the structure of the ribosome—an RNA-protein complex that catalyzes peptide bond formation—revealed that its active site is composed entirely of RNA. [7]

Structure

Watson-Crick base pairs in a siRNA (hydrogen atoms are not shown) Piwi-siRNA-basepairing.png
Watson-Crick base pairs in a siRNA (hydrogen atoms are not shown)

Each nucleotide in RNA contains a ribose sugar, with carbons numbered 1' through 5'. A base is attached to the 1' position, in general, adenine (A), cytosine (C), guanine (G), or uracil (U). Adenine and guanine are purines, cytosine and uracil are pyrimidines. A phosphate group is attached to the 3' position of one ribose and the 5' position of the next. The phosphate groups have a negative charge each, making RNA a charged molecule (polyanion). The bases form hydrogen bonds between cytosine and guanine, between adenine and uracil and between guanine and uracil. [8] However, other interactions are possible, such as a group of adenine bases binding to each other in a bulge, [9] or the GNRA tetraloop that has a guanine–adenine base-pair. [8]

Structure of a fragment of an RNA, showing a guanosyl subunit. RNA chemical structure.GIF
Structure of a fragment of an RNA, showing a guanosyl subunit.

An important structural component of RNA that distinguishes it from DNA is the presence of a hydroxyl group at the 2' position of the ribose sugar. The presence of this functional group causes the helix to mostly take the A-form geometry, [10] although in single strand dinucleotide contexts, RNA can rarely also adopt the B-form most commonly observed in DNA. [11] The A-form geometry results in a very deep and narrow major groove and a shallow and wide minor groove. [12] A second consequence of the presence of the 2'-hydroxyl group is that in conformationally flexible regions of an RNA molecule (that is, not involved in formation of a double helix), it can chemically attack the adjacent phosphodiester bond to cleave the backbone. [13]

Secondary structure of a telomerase RNA. Ciliate telomerase RNA.JPG
Secondary structure of a telomerase RNA.

RNA is transcribed with only four bases (adenine, cytosine, guanine and uracil), [14] but these bases and attached sugars can be modified in numerous ways as the RNAs mature. Pseudouridine (Ψ), in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond, and ribothymidine (T) are found in various places (the most notable ones being in the TΨC loop of tRNA). [15] Another notable modified base is hypoxanthine, a deaminated adenine base whose nucleoside is called inosine (I). Inosine plays a key role in the wobble hypothesis of the genetic code. [16]

There are more than 100 other naturally occurring modified nucleosides. [17] The greatest structural diversity of modifications can be found in tRNA, [18] while pseudouridine and nucleosides with 2'-O-methylribose often present in rRNA are the most common. [19] The specific roles of many of these modifications in RNA are not fully understood. However, it is notable that, in ribosomal RNA, many of the post-transcriptional modifications occur in highly functional regions, such as the peptidyl transferase center [20] and the subunit interface, implying that they are important for normal function. [21]

The functional form of single-stranded RNA molecules, just like proteins, frequently requires a specific tertiary structure. The scaffold for this structure is provided by secondary structural elements that are hydrogen bonds within the molecule. This leads to several recognizable "domains" of secondary structure like hairpin loops, bulges, and internal loops. [22] In order create, i.e., design, a RNA for any given secondary structure, two or three bases would not be enough, but four bases are enough. [23] This is likely why nature has "chosen" a four base alphabet: less than four does not allow to create all structures, while more than four bases are not necessary. Since RNA is charged, metal ions such as Mg2+ are needed to stabilise many secondary and tertiary structures. [24]

The naturally occurring enantiomer of RNA is D-RNA composed of D-ribonucleotides. All chirality centers are located in the D-ribose. By the use of L-ribose or rather L-ribonucleotides, L-RNA can be synthesized. L-RNA is much more stable against degradation by RNase. [25]

Like other structured biopolymers such as proteins, one can define topology of a folded RNA molecule. This is often done based on arrangement of intra-chain contacts within a folded RNA, termed as circuit topology.

Synthesis

Synthesis of RNA is usually catalyzed by an enzyme—RNA polymerase—using DNA as a template, a process known as transcription. Initiation of transcription begins with the binding of the enzyme to a promoter sequence in the DNA (usually found "upstream" of a gene). The DNA double helix is unwound by the helicase activity of the enzyme. The enzyme then progresses along the template strand in the 3’ to 5’ direction, synthesizing a complementary RNA molecule with elongation occurring in the 5’ to 3’ direction. The DNA sequence also dictates where termination of RNA synthesis will occur. [26]

Primary transcript RNAs are often modified by enzymes after transcription. For example, a poly(A) tail and a 5' cap are added to eukaryotic pre-mRNA and introns are removed by the spliceosome.

There are also a number of RNA-dependent RNA polymerases that use RNA as their template for synthesis of a new strand of RNA. For instance, a number of RNA viruses (such as poliovirus) use this type of enzyme to replicate their genetic material. [27] Also, RNA-dependent RNA polymerase is part of the RNA interference pathway in many organisms. [28]

Types of RNA

Overview

Structure of a hammerhead ribozyme, a ribozyme that cuts RNA Full length hammerhead ribozyme.png
Structure of a hammerhead ribozyme, a ribozyme that cuts RNA

Messenger RNA (mRNA) is the RNA that carries information from DNA to the ribosome, the sites of protein synthesis (translation) in the cell. The mRNA is a copy of DNA. The coding sequence of the mRNA determines the amino acid sequence in the protein that is produced. [29] However, many RNAs do not code for protein (about 97% of the transcriptional output is non-protein-coding in eukaryotes [30] [31] [32] [33] ).

These so-called non-coding RNAs ("ncRNA") can be encoded by their own genes (RNA genes), but can also derive from mRNA introns. [34] The most prominent examples of non-coding RNAs are transfer RNA (tRNA) and ribosomal RNA (rRNA), both of which are involved in the process of translation. [4] There are also non-coding RNAs involved in gene regulation, RNA processing and other roles. Certain RNAs are able to catalyse chemical reactions such as cutting and ligating other RNA molecules, [35] and the catalysis of peptide bond formation in the ribosome; [7] these are known as ribozymes.

In length

According to the length of RNA chain, RNA includes small RNA and long RNA. [36] Usually, small RNAs are shorter than 200  nt in length, and long RNAs are greater than 200  nt long. [37] Long RNAs, also called large RNAs, mainly include long non-coding RNA (lncRNA) and mRNA. Small RNAs mainly include 5.8S ribosomal RNA (rRNA), 5S rRNA, transfer RNA (tRNA), microRNA (miRNA), small interfering RNA (siRNA), small nucleolar RNA (snoRNAs), Piwi-interacting RNA (piRNA), tRNA-derived small RNA (tsRNA) [38] and small rDNA-derived RNA (srRNA). [39] There are certain exceptions as in the case of the 5S rRNA of the members of the genus Halococcus (Archaea), which have an insertion, thus increasing its size. [40] [41] [42]

In translation

Messenger RNA (mRNA) carries information about a protein sequence to the ribosomes, the protein synthesis factories in the cell. It is coded so that every three nucleotides (a codon) corresponds to one amino acid. In eukaryotic cells, once precursor mRNA (pre-mRNA) has been transcribed from DNA, it is processed to mature mRNA. This removes its introns—non-coding sections of the pre-mRNA. The mRNA is then exported from the nucleus to the cytoplasm, where it is bound to ribosomes and translated into its corresponding protein form with the help of tRNA. In prokaryotic cells, which do not have nucleus and cytoplasm compartments, mRNA can bind to ribosomes while it is being transcribed from DNA. After a certain amount of time, the message degrades into its component nucleotides with the assistance of ribonucleases. [29]

Transfer RNA (tRNA) is a small RNA chain of about 80 nucleotides that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation. It has sites for amino acid attachment and an anticodon region for codon recognition that binds to a specific sequence on the messenger RNA chain through hydrogen bonding. [34]

Ribosomal RNA (rRNA) is the catalytic component of the ribosomes. The rRNA is the component of the ribosome that hosts translation. Eukaryotic ribosomes contain four different rRNA molecules: 18S, 5.8S, 28S and 5S rRNA. Three of the rRNA molecules are synthesized in the nucleolus, and one is synthesized elsewhere. In the cytoplasm, ribosomal RNA and protein combine to form a nucleoprotein called a ribosome. The ribosome binds mRNA and carries out protein synthesis. Several ribosomes may be attached to a single mRNA at any time. [29] Nearly all the RNA found in a typical eukaryotic cell is rRNA.

Transfer-messenger RNA (tmRNA) is found in many bacteria and plastids. It tags proteins encoded by mRNAs that lack stop codons for degradation and prevents the ribosome from stalling. [43]

Regulatory RNA

The earliest known regulators of gene expression were proteins known as repressors and activators – regulators with specific short binding sites within enhancer regions near the genes to be regulated. [44]   Later studies have shown that RNAs also regulate genes. There are several kinds of RNA-dependent processes in eukaryotes regulating the expression of genes at various points, such as RNAi repressing genes post-transcriptionally, long non-coding RNAs shutting down blocks of chromatin epigenetically, and enhancer RNAs inducing increased gene expression. [45] Bacteria and archaea have also been shown to use regulatory RNA systems such as bacterial small RNAs and CRISPR. [46] Fire and Mello were awarded the 2006 Nobel Prize in Physiology or Medicine for discovering microRNAs (miRNAs), specific short RNA molecules that can base-pair with mRNAs. [47]

RNA interference by miRNAs

Post-transcriptional expression levels of many genes can be controlled by RNA interference, in which miRNAs, specific short RNA molecules, pair with mRNA regions and target them for degradation. [48] This antisense-based process involves steps that first process the RNA so that it can base-pair with a region of its target mRNAs. Once the base pairing occurs, other proteins direct the mRNA to be destroyed by nucleases. [45]

Long non-coding RNAs

Next to be linked to regulation were Xist and other long noncoding RNAs associated with X chromosome inactivation.  Their roles, at first mysterious, were shown by Jeannie T. Lee and others to be the silencing of blocks of chromatin via recruitment of Polycomb complex so that messenger RNA could not be transcribed from them. [49] Additional lncRNAs, currently defined as RNAs of more than 200 base pairs that do not appear to have coding potential, [50] have been found associated with regulation of stem cell pluripotency and cell division. [50]

Enhancer RNAs

The third major group of regulatory RNAs is called enhancer RNAs. [50]  It is not clear at present whether they are a unique category of RNAs of various lengths or constitute a distinct subset of lncRNAs.  In any case, they are transcribed from enhancers, which are known regulatory sites in the DNA near genes they regulate. [50] [51]  They up-regulate the transcription of the gene(s) under control of the enhancer from which they are transcribed. [50] [52]

Regulatory RNA in prokaryotes

At first, regulatory RNA was thought to be a eukaryotic phenomenon, a part of the explanation for why so much more transcription in higher organisms was seen than had been predicted. But as soon as researchers began to look for possible RNA regulators in bacteria, they turned up there as well, termed as small RNA (sRNA). [53] [46] Currently, the ubiquitous nature of systems of RNA regulation of genes has been discussed as support for the RNA World theory. [45] [54] Bacterial small RNAs generally act via antisense pairing with mRNA to down-regulate its translation, either by affecting stability or affecting cis-binding ability. [45] Riboswitches have also been discovered. They are cis-acting regulatory RNA sequences acting allosterically. They change shape when they bind metabolites so that they gain or lose the ability to bind chromatin to regulate expression of genes. [55] [56]

Archaea also have systems of regulatory RNA. [57] The CRISPR system, recently being used to edit DNA in situ, acts via regulatory RNAs in archaea and bacteria to provide protection against virus invaders. [45] [58]

In RNA processing

Uridine to pseudouridine is a common RNA modification. Synthesis of Pseudouridine.svg
Uridine to pseudouridine is a common RNA modification.

Many RNAs are involved in modifying other RNAs. Introns are spliced out of pre-mRNA by spliceosomes, which contain several small nuclear RNAs (snRNA), [4] or the introns can be ribozymes that are spliced by themselves. [59] RNA can also be altered by having its nucleotides modified to nucleotides other than A, C, G and U. In eukaryotes, modifications of RNA nucleotides are in general directed by small nucleolar RNAs (snoRNA; 60–300 nt), [34] found in the nucleolus and cajal bodies. snoRNAs associate with enzymes and guide them to a spot on an RNA by basepairing to that RNA. These enzymes then perform the nucleotide modification. rRNAs and tRNAs are extensively modified, but snRNAs and mRNAs can also be the target of base modification. [60] [61] RNA can also be methylated. [62] [63]

RNA genomes

Like DNA, RNA can carry genetic information. RNA viruses have genomes composed of RNA that encodes a number of proteins. The viral genome is replicated by some of those proteins, while other proteins protect the genome as the virus particle moves to a new host cell. Viroids are another group of pathogens, but they consist only of RNA, do not encode any protein and are replicated by a host plant cell's polymerase. [64]

In reverse transcription

Reverse transcribing viruses replicate their genomes by reverse transcribing DNA copies from their RNA; these DNA copies are then transcribed to new RNA. Retrotransposons also spread by copying DNA and RNA from one another, [65] and telomerase contains an RNA that is used as template for building the ends of eukaryotic chromosomes. [66]

Double-stranded RNA

Double-stranded RNA Double-stranded RNA.gif
Double-stranded RNA

Double-stranded RNA (dsRNA) is RNA with two complementary strands, similar to the DNA found in all cells, but with the replacement of thymine by uracil and the adding of one oxygen atom. dsRNA forms the genetic material of some viruses (double-stranded RNA viruses). Double-stranded RNA, such as viral RNA or siRNA, can trigger RNA interference in eukaryotes, as well as interferon response in vertebrates. [67] [68] [69] [70] In Eukaryotes, Double-stranded RNA (dsRNA) plays a role in the activation of the innate immune system against viral infections. [71]

Circular RNA

In the late 1970s, it was shown that there is a single stranded covalently closed, i.e. circular form of RNA expressed throughout the animal and plant kingdom (see circRNA). [72] circRNAs are thought to arise via a "back-splice" reaction where the spliceosome joins a upstream 3' acceptor to a downstream 5' donor splice site. So far the function of circRNAs is largely unknown, although for few examples a microRNA sponging activity has been demonstrated.

Key discoveries in RNA biology

Robert W. Holley, left, poses with his research team. R Holley.jpg
Robert W. Holley, left, poses with his research team.

Research on RNA has led to many important biological discoveries and numerous Nobel Prizes. Nucleic acids were discovered in 1868 by Friedrich Miescher, who called the material 'nuclein' since it was found in the nucleus. [73] It was later discovered that prokaryotic cells, which do not have a nucleus, also contain nucleic acids. The role of RNA in protein synthesis was suspected already in 1939. [74] Severo Ochoa won the 1959 Nobel Prize in Medicine (shared with Arthur Kornberg) after he discovered an enzyme that can synthesize RNA in the laboratory. [75] However, the enzyme discovered by Ochoa (polynucleotide phosphorylase) was later shown to be responsible for RNA degradation, not RNA synthesis. In 1956 Alex Rich and David Davies hybridized two separate strands of RNA to form the first crystal of RNA whose structure could be determined by X-ray crystallography. [76]

The sequence of the 77 nucleotides of a yeast tRNA was found by Robert W. Holley in 1965, [77] winning Holley the 1968 Nobel Prize in Medicine (shared with Har Gobind Khorana and Marshall Nirenberg).

In the early 1970s, retroviruses and reverse transcriptase were discovered, showing for the first time that enzymes could copy RNA into DNA (the opposite of the usual route for transmission of genetic information). For this work, David Baltimore, Renato Dulbecco and Howard Temin were awarded a Nobel Prize in 1975. In 1976, Walter Fiers and his team determined the first complete nucleotide sequence of an RNA virus genome, that of bacteriophage MS2. [78]

In 1977, introns and RNA splicing were discovered in both mammalian viruses and in cellular genes, resulting in a 1993 Nobel to Philip Sharp and Richard Roberts. Catalytic RNA molecules (ribozymes) were discovered in the early 1980s, leading to a 1989 Nobel award to Thomas Cech and Sidney Altman. In 1990, it was found in Petunia that introduced genes can silence similar genes of the plant's own, now known to be a result of RNA interference. [79] [80]

At about the same time, 22 nt long RNAs, now called microRNAs, were found to have a role in the development of C. elegans . [81] Studies on RNA interference gleaned a Nobel Prize for Andrew Fire and Craig Mello in 2006, and another Nobel was awarded for studies on the transcription of RNA to Roger Kornberg in the same year. The discovery of gene regulatory RNAs has led to attempts to develop drugs made of RNA, such as siRNA, to silence genes. [82] Adding to the Nobel prizes awarded for research on RNA in 2009 it was awarded for the elucidation of the atomic structure of the ribosome to Venki Ramakrishnan, Thomas A. Steitz, and Ada Yonath.

Relevance for prebiotic chemistry and abiogenesis

In 1968, Carl Woese hypothesized that RNA might be catalytic and suggested that the earliest forms of life (self-replicating molecules) could have relied on RNA both to carry genetic information and to catalyze biochemical reactions—an RNA world. [83] [84] In May 2022, scientists reported that they discovered RNA forms spontaneously on prebiotic basalt lava glass which is presumed to have been abundantly available on the early Earth. [85] [86]

In March 2015, complex DNA and RNA nucleotides, including uracil, cytosine and thymine, were reportedly formed in the laboratory under outer space conditions, using starter chemicals, such as pyrimidine, an organic compound commonly found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), is one of the most carbon-rich compounds found in the Universe and may have been formed in red giants or in interstellar dust and gas clouds. [87] In July 2022, astronomers reported the discovery of massive amounts of prebiotic molecules, including possible RNA precursors, in the Galactic Center of the Milky Way Galaxy. [88] [89]

See also

Related Research Articles

<span class="mw-page-title-main">Nucleic acid</span> Class of large biomolecules essential to all known life

Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is the ribose derivative deoxyribose, the polymer is DNA.

<span class="mw-page-title-main">Nucleotide</span> Biological molecules that form the building blocks of nucleic acids

Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

<span class="mw-page-title-main">Protein biosynthesis</span> Assembly of proteins inside biological cells

Protein biosynthesis is a core biological process, occurring inside cells, balancing the loss of cellular proteins through the production of new proteins. Proteins perform a number of critical functions as enzymes, structural proteins or hormones. Protein synthesis is a very similar process for both prokaryotes and eukaryotes but there are some distinct differences.

<span class="mw-page-title-main">RNA world</span> Hypothetical stage in the early evolutionary history of life on Earth

The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence of this stage.

<span class="mw-page-title-main">Ribosome</span> Intracellular organelle consisting of RNA and protein functioning to synthesize proteins

Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis. Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA (rRNA) molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.

<span class="mw-page-title-main">Central dogma of molecular biology</span> Explanation of the flow of genetic information within a biological system

The central dogma of molecular biology is an explanation of the flow of genetic information within a biological system. It is often stated as "DNA makes RNA, and RNA makes protein", although this is not its original meaning. It was first stated by Francis Crick in 1957, then published in 1958:

The Central Dogma. This states that once "information" has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.

<span class="mw-page-title-main">Nucleobase</span> Nitrogen-containing biological compounds that form nucleosides

Nucleobases, also known as nitrogenous bases or often simply bases, are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Five nucleobases—adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U)—are called primary or canonical. They function as the fundamental units of the genetic code, with the bases A, G, C, and T being found in DNA while A, G, C, and U are found in RNA. Thymine and uracil are distinguished by merely the presence or absence of a methyl group on the fifth carbon (C5) of these heterocyclic six-membered rings. In addition, some viruses have aminoadenine (Z) instead of adenine. It differs in having an extra amine group, creating a more stable bond to thymine.

<span class="mw-page-title-main">RNA polymerase</span> Enzyme that synthesizes RNA from DNA

In molecular biology, RNA polymerase, or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template.

<span class="mw-page-title-main">Ribozyme</span> Type of RNA molecules

Ribozymes are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982, discovery of ribozymes demonstrated that RNA can be both genetic material and a biological catalyst, and contributed to the RNA world hypothesis, which suggests that RNA may have been important in the evolution of prebiotic self-replicating systems.

<span class="mw-page-title-main">Translation (biology)</span> Cellular process of protein synthesis

In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or endoplasmic reticulum synthesize proteins after the process of transcription of DNA to RNA in the cell's nucleus. The entire process is called gene expression.

<span class="mw-page-title-main">Nucleic acid sequence</span> Succession of nucleotides in a nucleic acid

A nucleic acid sequence is a succession of bases signified by a series of a set of five different letters that indicate the order of nucleotides forming alleles within a DNA or RNA (GACU) molecule. By convention, sequences are usually presented from the 5' end to the 3' end. For DNA, the sense strand is used. Because nucleic acids are normally linear (unbranched) polymers, specifying the sequence is equivalent to defining the covalent structure of the entire molecule. For this reason, the nucleic acid sequence is also termed the primary structure.

<span class="mw-page-title-main">Ribonucleotide</span> Nucleotide containing ribose as its pentose component

In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecular precursor of nucleic acids. Nucleotides are the basic building blocks of DNA and RNA. Ribonucleotides themselves are basic monomeric building blocks for RNA. Deoxyribonucleotides, formed by reducing ribonucleotides with the enzyme ribonucleotide reductase (RNR), are essential building blocks for DNA. There are several differences between DNA deoxyribonucleotides and RNA ribonucleotides. Successive nucleotides are linked together via phosphodiester bonds.

A nucleoside triphosphate is a nucleoside containing a nitrogenous base bound to a 5-carbon sugar, with three phosphate groups bound to the sugar. They are the molecular precursors of both DNA and RNA, which are chains of nucleotides made through the processes of DNA replication and transcription. Nucleoside triphosphates also serve as a source of energy for cellular reactions and are involved in signalling pathways.

<span class="mw-page-title-main">Ribosomal RNA</span> RNA component of the ribosome, essential for protein synthesis in all living organisms

Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits. rRNA is the physical and mechanical factor of the ribosome that forces transfer RNA (tRNA) and messenger RNA (mRNA) to process and translate the latter into proteins. Ribosomal RNA is the predominant form of RNA found in most cells; it makes up about 80% of cellular RNA despite never being translated into proteins itself. Ribosomes are composed of approximately 60% rRNA and 40% ribosomal proteins by mass.

The history of molecular biology begins in the 1930s with the convergence of various, previously distinct biological and physical disciplines: biochemistry, genetics, microbiology, virology and physics. With the hope of understanding life at its most fundamental level, numerous physicists and chemists also took an interest in what would become molecular biology.

In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, sense may have slightly different meanings. For example, negative-sense strand of DNA is equivalent to the template strand, whereas the positive-sense strand is the non-template strand whose nucleotide sequence is equivalent to the sequence of the mRNA transcript.

Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can be programmed by the nucleotide sequence of the mRNA and is sometimes affected by the secondary, 3-dimensional mRNA structure. It has been described mainly in viruses, retrotransposons and bacterial insertion elements, and also in some cellular genes.

Numerous key discoveries in biology have emerged from studies of RNA, including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.

<span class="mw-page-title-main">Nucleic acid quaternary structure</span>

Nucleic acidquaternary structure refers to the interactions between separate nucleic acid molecules, or between nucleic acid molecules and proteins. The concept is analogous to protein quaternary structure, but as the analogy is not perfect, the term is used to refer to a number of different concepts in nucleic acids and is less commonly encountered. Similarly other biomolecules such as proteins, nucleic acids have four levels of structural arrangement: primary, secondary, tertiary, and quaternary structure. Primary structure is the linear sequence of nucleotides, secondary structure involves small local folding motifs, and tertiary structure is the 3D folded shape of nucleic acid molecule. In general, quaternary structure refers to 3D interactions between multiple subunits. In the case of nucleic acids, quaternary structure refers to interactions between multiple nucleic acid molecules or between nucleic acids and proteins. Nucleic acid quaternary structure is important for understanding DNA, RNA, and gene expression because quaternary structure can impact function. For example, when DNA is packed into chromatin, therefore exhibiting a type of quaternary structure, gene transcription will be inhibited.

This glossary of genetics is a list of definitions of terms and concepts commonly used in the study of genetics and related disciplines in biology, including molecular biology, cell biology, and evolutionary biology. It is intended as introductory material for novices; for more specific and technical detail, see the article corresponding to each term. For related terms, see Glossary of evolutionary biology.

References

  1. "RNA: The Versatile Molecule". University of Utah. 2015.
  2. "Nucleotides and Nucleic Acids" (PDF). University of California, Los Angeles. Archived from the original (PDF) on 2015-09-23. Retrieved 2015-08-26.
  3. Shukla RN (2014). Analysis of Chromosomes. ISBN   978-93-84568-17-7.
  4. 1 2 3 Berg JM, Tymoczko JL, Stryer L (2002). Biochemistry (5th ed.). WH Freeman and Company. pp. 118–19, 781–808. ISBN   978-0-7167-4684-3. OCLC   179705944.
  5. Tinoco I, Bustamante C (October 1999). "How RNA folds". Journal of Molecular Biology. 293 (2): 271–81. doi:10.1006/jmbi.1999.3001. PMID   10550208.
  6. Higgs PG (August 2000). "RNA secondary structure: physical and computational aspects". Quarterly Reviews of Biophysics. 33 (3): 199–253. doi:10.1017/S0033583500003620. PMID   11191843. S2CID   37230785.
  7. 1 2 Nissen P, Hansen J, Ban N, Moore PB, Steitz TA (August 2000). "The structural basis of ribosome activity in peptide bond synthesis". Science. 289 (5481): 920–30. Bibcode:2000Sci...289..920N. doi:10.1126/science.289.5481.920. PMID   10937990.
  8. 1 2 Lee JC, Gutell RR (December 2004). "Diversity of base-pair conformations and their occurrence in rRNA structure and RNA structural motifs". Journal of Molecular Biology. 344 (5): 1225–49. doi:10.1016/j.jmb.2004.09.072. PMID   15561141.
  9. Barciszewski J, Frederic B, Clark C (1999). RNA biochemistry and biotechnology. Springer. pp. 73–87. ISBN   978-0-7923-5862-6. OCLC   52403776.
  10. Salazar M, Fedoroff OY, Miller JM, Ribeiro NS, Reid BR (April 1993). "The DNA strand in DNA.RNA hybrid duplexes is neither B-form nor A-form in solution". Biochemistry. 32 (16): 4207–15. doi:10.1021/bi00067a007. PMID   7682844.
  11. Sedova A, Banavali NK (February 2016). "RNA approaches the B-form in stacked single strand dinucleotide contexts". Biopolymers. 105 (2): 65–82. doi:10.1002/bip.22750. PMID   26443416. S2CID   35949700.
  12. Hermann T, Patel DJ (March 2000). "RNA bulges as architectural and recognition motifs". Structure. 8 (3): R47–54. doi: 10.1016/S0969-2126(00)00110-6 . PMID   10745015.
  13. Mikkola S, Stenman E, Nurmi K, Yousefi-Salakdeh E, Strömberg R, Lönnberg H (1999). "The mechanism of the metal ion promoted cleavage of RNA phosphodiester bonds involves a general acid catalysis by the metal aquo ion on the departure of the leaving group". Journal of the Chemical Society, Perkin Transactions 2 (8): 1619–26. doi:10.1039/a903691a.
  14. Jankowski JA, Polak JM (1996). Clinical gene analysis and manipulation: Tools, techniques and troubleshooting. Cambridge University Press. p.  14. ISBN   978-0-521-47896-0. OCLC   33838261.
  15. Yu Q, Morrow CD (May 2001). "Identification of critical elements in the tRNA acceptor stem and T(Psi)C loop necessary for human immunodeficiency virus type 1 infectivity". Journal of Virology. 75 (10): 4902–6. doi:10.1128/JVI.75.10.4902-4906.2001. PMC   114245 . PMID   11312362.
  16. Elliott MS, Trewyn RW (February 1984). "Inosine biosynthesis in transfer RNA by an enzymatic insertion of hypoxanthine". The Journal of Biological Chemistry. 259 (4): 2407–10. doi: 10.1016/S0021-9258(17)43367-9 . PMID   6365911.
  17. Cantara WA, Crain PF, Rozenski J, McCloskey JA, Harris KA, Zhang X, Vendeix FA, Fabris D, Agris PF (January 2011). "The RNA Modification Database, RNAMDB: 2011 update". Nucleic Acids Research. 39 (Database issue): D195-201. doi:10.1093/nar/gkq1028. PMC   3013656 . PMID   21071406.
  18. Söll D, RajBhandary U (1995). TRNA: Structure, biosynthesis, and function. ASM Press. p. 165. ISBN   978-1-55581-073-3. OCLC   183036381.
  19. Kiss T (July 2001). "Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs". The EMBO Journal. 20 (14): 3617–22. doi:10.1093/emboj/20.14.3617. PMC   125535 . PMID   11447102.
  20. Tirumalai MR, Rivas M, Tran Q, Fox GE (November 2021). "The Peptidyl Transferase Center: a Window to the Past". Microbiol Mol Biol Rev. 85 (4): e0010421. doi:10.1128/MMBR.00104-21. PMC   8579967 . PMID   34756086.
  21. King TH, Liu B, McCully RR, Fournier MJ (February 2003). "Ribosome structure and activity are altered in cells lacking snoRNPs that form pseudouridines in the peptidyl transferase center". Molecular Cell. 11 (2): 425–35. doi: 10.1016/S1097-2765(03)00040-6 . PMID   12620230.
  22. Mathews DH, Disney MD, Childs JL, Schroeder SJ, Zuker M, Turner DH (May 2004). "Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure". Proceedings of the National Academy of Sciences of the United States of America. 101 (19): 7287–92. Bibcode:2004PNAS..101.7287M. doi: 10.1073/pnas.0401799101 . PMC   409911 . PMID   15123812.
  23. Burghardt B, Hartmann AK (February 2007). "RNA secondary structure design". Physical Review E. 75 (2): 021920. arXiv: physics/0609135 . Bibcode:2007PhRvE..75b1920B. doi:10.1103/PhysRevE.75.021920. PMID   17358380. S2CID   17574854.
  24. Tan ZJ, Chen SJ (July 2008). "Salt dependence of nucleic acid hairpin stability". Biophysical Journal. 95 (2): 738–52. Bibcode:2008BpJ....95..738T. doi:10.1529/biophysj.108.131524. PMC   2440479 . PMID   18424500.
  25. Vater A, Klussmann S (January 2015). "Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer(®) therapeutics". Drug Discovery Today. 20 (1): 147–55. doi: 10.1016/j.drudis.2014.09.004 . PMID   25236655.
  26. Nudler E, Gottesman ME (August 2002). "Transcription termination and anti-termination in E. coli". Genes to Cells. 7 (8): 755–68. doi: 10.1046/j.1365-2443.2002.00563.x . PMID   12167155. S2CID   23191624.
  27. Hansen JL, Long AM, Schultz SC (August 1997). "Structure of the RNA-dependent RNA polymerase of poliovirus". Structure. 5 (8): 1109–22. doi: 10.1016/S0969-2126(97)00261-X . PMID   9309225.
  28. Ahlquist P (May 2002). "RNA-dependent RNA polymerases, viruses, and RNA silencing". Science. 296 (5571): 1270–73. Bibcode:2002Sci...296.1270A. doi:10.1126/science.1069132. PMID   12016304. S2CID   42526536.
  29. 1 2 3 Cooper GC, Hausman RE (2004). The Cell: A Molecular Approach (3rd ed.). Sinauer. pp. 261–76, 297, 339–44. ISBN   978-0-87893-214-6. OCLC   174924833.
  30. Mattick JS, Gagen MJ (September 2001). "The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms". Molecular Biology and Evolution. 18 (9): 1611–30. doi: 10.1093/oxfordjournals.molbev.a003951 . PMID   11504843.
  31. Mattick JS (November 2001). "Non-coding RNAs: the architects of eukaryotic complexity". EMBO Reports. 2 (11): 986–91. doi:10.1093/embo-reports/kve230. PMC   1084129 . PMID   11713189.
  32. Mattick JS (October 2003). "Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms" (PDF). BioEssays. 25 (10): 930–39. CiteSeerX   10.1.1.476.7561 . doi:10.1002/bies.10332. PMID   14505360. Archived from the original (PDF) on 2009-03-06.
  33. Mattick JS (October 2004). "The hidden genetic program of complex organisms". Scientific American. 291 (4): 60–67. Bibcode:2004SciAm.291d..60M. doi:10.1038/scientificamerican1004-60. PMID   15487671.[ dead link ]
  34. 1 2 3 Wirta W (2006). Mining the transcriptome – methods and applications. Stockholm: School of Biotechnology, Royal Institute of Technology. ISBN   978-91-7178-436-0. OCLC   185406288.
  35. Rossi JJ (July 2004). "Ribozyme diagnostics comes of age". Chemistry & Biology. 11 (7): 894–95. doi: 10.1016/j.chembiol.2004.07.002 . PMID   15271347.
  36. Storz G (May 2002). "An expanding universe of noncoding RNAs". Science. 296 (5571): 1260–63. Bibcode:2002Sci...296.1260S. doi:10.1126/science.1072249. PMID   12016301. S2CID   35295924.
  37. Fatica A, Bozzoni I (January 2014). "Long non-coding RNAs: new players in cell differentiation and development". Nature Reviews Genetics. 15 (1): 7–21. doi:10.1038/nrg3606. PMID   24296535. S2CID   12295847.[ permanent dead link ]
  38. Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, et al. (January 2016). "Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder" (PDF). Science. 351 (6271): 397–400. Bibcode:2016Sci...351..397C. doi:10.1126/science.aad7977. PMID   26721680. S2CID   21738301.
  39. Wei H, Zhou B, Zhang F, Tu Y, Hu Y, Zhang B, Zhai Q (2013). "Profiling and identification of small rDNA-derived RNAs and their potential biological functions". PLOS ONE. 8 (2): e56842. Bibcode:2013PLoSO...856842W. doi: 10.1371/journal.pone.0056842 . PMC   3572043 . PMID   23418607.
  40. Luehrsen KR, Nicholson DE, Eubanks DC, Fox GE (1981). "An archaebacterial 5S rRNA contains a long insertion sequence". Nature. 293 (5835): 755–756. Bibcode:1981Natur.293..755L. doi:10.1038/293755a0. PMID   6169998. S2CID   4341755.
  41. Stan-Lotter H, McGenity TJ, Legat A, Denner EB, Glaser K, Stetter KO, Wanner G (1999). "Very similar strains of Halococcus salifodinae are found in geographically separated permo-triassic salt deposits". Microbiology. 145 (Pt 12): 3565–3574. doi: 10.1099/00221287-145-12-3565 . PMID   10627054.
  42. Tirumalai MR, Kaelber JT, Park DR, Tran Q, Fox GE (August 2020). "Cryo-Electron Microscopy Visualization of a Large Insertion in the 5S ribosomal RNA of the Extremely Halophilic Archaeon Halococcus morrhuae". FEBS Open Bio. 10 (10): 1938–1946. doi:10.1002/2211-5463.12962. PMC   7530397 . PMID   32865340.
  43. Gueneau de Novoa P, Williams KP (January 2004). "The tmRNA website: reductive evolution of tmRNA in plastids and other endosymbionts". Nucleic Acids Research. 32 (Database issue): D104–08. doi:10.1093/nar/gkh102. PMC   308836 . PMID   14681369.
  44. Jacob F, Monod J (1961). "Genetic Regulatory Mechanisms in the Synthesis of Proteins". Journal of Molecular Biology. 3 (3): 318–56. doi:10.1016/s0022-2836(61)80072-7. PMID   13718526.
  45. 1 2 3 4 5 Morris K, Mattick J (2014). "The rise of regulatory RNA". Nature Reviews Genetics. 15 (6): 423–37. doi:10.1038/nrg3722. PMC   4314111 . PMID   24776770.
  46. 1 2 Gottesman S (2005). "Micros for microbes: non-coding regulatory RNAs in bacteria". Trends in Genetics. 21 (7): 399–404. doi:10.1016/j.tig.2005.05.008. PMID   15913835.
  47. "The Nobel Prize in Physiology or Medicine 2006". Nobelprize.org. Nobel Media AB 2014. Web. 6 Aug 2018. http://www.nobelprize.org/nobel_prizes/medicine/laureates/2006
  48. Fire, et al. (1998). "Potent and Specific Genetic Interference by double stranded RNA in Ceanorhabditis elegans". Nature. 391 (6669): 806–11. Bibcode:1998Natur.391..806F. doi:10.1038/35888. PMID   9486653. S2CID   4355692.
  49. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT (2008). "Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome". Science. 322 (5902): 750–56. Bibcode:2008Sci...322..750Z. doi:10.1126/science.1163045. PMC   2748911 . PMID   18974356.
  50. 1 2 3 4 5 Rinn JL, Chang HY (2012). "Genome regulation by long noncoding RNAs". Annu. Rev. Biochem. 81: 1–25. doi:10.1146/annurev-biochem-051410-092902. PMC   3858397 . PMID   22663078.
  51. Taft RJ, Kaplan CD, Simons C, Mattick JS (2009). "Evolution, biogenesis and function of promoter- associated RNAs". Cell Cycle. 8 (15): 2332–38. doi: 10.4161/cc.8.15.9154 . PMID   19597344.
  52. Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, et al. (2010). "'Long noncoding RNAs with enhancer-like function in human cells". Cell. 143 (1): 46–58. doi:10.1016/j.cell.2010.09.001. PMC   4108080 . PMID   20887892.
  53. EGH Wagner, P Romby. (2015). "Small RNAs in bacteria and archaea: who they are, what they do, and how they do it". Advances in genetics (Vol. 90, pp. 133–208).
  54. J.W. Nelson, R.R. Breaker (2017) "The lost language of the RNA World."Sci. Signal.10,eaam8812 1–11.
  55. Winklef WC (2005). "Riboswitches and the role of noncoding RNAs in bacterial metabolic control". Curr. Opin. Chem. Biol. 9 (6): 594–602. doi:10.1016/j.cbpa.2005.09.016. PMID   16226486.
  56. Tucker BJ, Breaker RR (2005). "Riboswitches as versatile gene control elements". Curr. Opin. Struct. Biol. 15 (3): 342–48. doi:10.1016/j.sbi.2005.05.003. PMID   15919195.
  57. Mojica FJ, Diez-Villasenor C, Soria E, Juez G (2000). "" "Biological significance of a family of regularly spaced repeats in the genomes of archaea, bacteria and mitochondria". Mol. Microbiol. 36 (1): 244–46. doi: 10.1046/j.1365-2958.2000.01838.x . PMID   10760181. S2CID   22216574.
  58. Brouns S, Jore MM, Lundgren M, Westra E, Slijkhuis R, Snijders A, Dickman M, Makarova K, Koonin E, Der Oost JV (2008). "Small CRISPR RNAs guide antiviral defense in prokaryotes". Science. 321 (5891): 960–64. Bibcode:2008Sci...321..960B. doi:10.1126/science.1159689. PMC   5898235 . PMID   18703739.
  59. Steitz TA, Steitz JA (July 1993). "A general two-metal-ion mechanism for catalytic RNA". Proceedings of the National Academy of Sciences of the United States of America. 90 (14): 6498–502. Bibcode:1993PNAS...90.6498S. doi: 10.1073/pnas.90.14.6498 . PMC   46959 . PMID   8341661.
  60. Xie J, Zhang M, Zhou T, Hua X, Tang L, Wu W (January 2007). "Sno/scaRNAbase: a curated database for small nucleolar RNAs and cajal body-specific RNAs". Nucleic Acids Research. 35 (Database issue): D183–87. doi:10.1093/nar/gkl873. PMC   1669756 . PMID   17099227.
  61. Omer AD, Ziesche S, Decatur WA, Fournier MJ, Dennis PP (May 2003). "RNA-modifying machines in archaea". Molecular Microbiology. 48 (3): 617–29. doi: 10.1046/j.1365-2958.2003.03483.x . PMID   12694609. S2CID   20326977.
  62. Cavaillé J, Nicoloso M, Bachellerie JP (October 1996). "Targeted ribose methylation of RNA in vivo directed by tailored antisense RNA guides". Nature. 383 (6602): 732–35. Bibcode:1996Natur.383..732C. doi: 10.1038/383732a0 . PMID   8878486. S2CID   4334683.
  63. Kiss-László Z, Henry Y, Bachellerie JP, Caizergues-Ferrer M, Kiss T (June 1996). "Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs". Cell. 85 (7): 1077–88. doi: 10.1016/S0092-8674(00)81308-2 . PMID   8674114. S2CID   10418885.
  64. Daròs JA, Elena SF, Flores R (June 2006). "Viroids: an Ariadne's thread into the RNA labyrinth". EMBO Reports. 7 (6): 593–98. doi:10.1038/sj.embor.7400706. PMC   1479586 . PMID   16741503.
  65. Kalendar R, Vicient CM, Peleg O, Anamthawat-Jonsson K, Bolshoy A, Schulman AH (March 2004). "Large retrotransposon derivatives: abundant, conserved but nonautonomous retroelements of barley and related genomes". Genetics. 166 (3): 1437–50. doi:10.1534/genetics.166.3.1437. PMC   1470764 . PMID   15082561.
  66. Podlevsky JD, Bley CJ, Omana RV, Qi X, Chen JJ (January 2008). "The telomerase database". Nucleic Acids Research. 36 (Database issue): D339–43. doi:10.1093/nar/gkm700. PMC   2238860 . PMID   18073191.
  67. Blevins T, Rajeswaran R, Shivaprasad PV, Beknazariants D, Si-Ammour A, Park HS, Vazquez F, Robertson D, Meins F, Hohn T, Pooggin MM (2006). "Four plant Dicers mediate viral small RNA biogenesis and DNA virus induced silencing". Nucleic Acids Research. 34 (21): 6233–46. doi:10.1093/nar/gkl886. PMC   1669714 . PMID   17090584.
  68. Jana S, Chakraborty C, Nandi S, Deb JK (November 2004). "RNA interference: potential therapeutic targets". Applied Microbiology and Biotechnology. 65 (6): 649–57. doi:10.1007/s00253-004-1732-1. PMID   15372214. S2CID   20963666.
  69. Virol, J (May 2006). "Double-Stranded RNA Is Produced by Positive-Strand RNA Viruses and DNA Viruses but Not in Detectable Amounts by Negative-Strand RNA Viruses". Journal of Virology. 80 (10): 5059–5064. doi:10.1128/JVI.80.10.5059-5064.2006. PMC   1472073 . PMID   16641297.
  70. Schultz U, Kaspers B, Staeheli P (May 2004). "The interferon system of non-mammalian vertebrates". Developmental and Comparative Immunology. 28 (5): 499–508. doi:10.1016/j.dci.2003.09.009. PMID   15062646.
  71. Whitehead KA, Dahlman JE, Langer RS, Anderson DG (2011). "Silencing or stimulation? siRNA delivery and the immune system". Annual Review of Chemical and Biomolecular Engineering. 2: 77–96. doi:10.1146/annurev-chembioeng-061010-114133. PMID   22432611.
  72. Hsu MT, Coca-Prados M (July 1979). "Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells". Nature. 280 (5720): 339–40. Bibcode:1979Natur.280..339H. doi:10.1038/280339a0. PMID   460409. S2CID   19968869.
  73. Dahm R (February 2005). "Friedrich Miescher and the discovery of DNA". Developmental Biology. 278 (2): 274–88. doi: 10.1016/j.ydbio.2004.11.028 . PMID   15680349.
  74. Caspersson T, Schultz J (1939). "Pentose nucleotides in the cytoplasm of growing tissues". Nature. 143 (3623): 602–03. Bibcode:1939Natur.143..602C. doi:10.1038/143602c0. S2CID   4140563.
  75. Ochoa S (1959). "Enzymatic synthesis of ribonucleic acid" (PDF). Nobel Lecture.
  76. Rich A, Davies D (1956). "A New Two-Stranded Helical Structure: Polyadenylic Acid and Polyuridylic Acid". Journal of the American Chemical Society. 78 (14): 3548–49. doi:10.1021/ja01595a086.
  77. Holley RW, et al. (March 1965). "Structure of a ribonucleic acid". Science. 147 (3664): 1462–65. Bibcode:1965Sci...147.1462H. doi:10.1126/science.147.3664.1462. PMID   14263761. S2CID   40989800.
  78. Fiers W, et al. (April 1976). "Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene". Nature. 260 (5551): 500–07. Bibcode:1976Natur.260..500F. doi:10.1038/260500a0. PMID   1264203. S2CID   4289674.
  79. Napoli C, Lemieux C, Jorgensen R (April 1990). "Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans". The Plant Cell. 2 (4): 279–89. doi:10.1105/tpc.2.4.279. PMC   159885 . PMID   12354959.
  80. Dafny-Yelin M, Chung SM, Frankman EL, Tzfira T (December 2007). "pSAT RNA interference vectors: a modular series for multiple gene down-regulation in plants". Plant Physiology. 145 (4): 1272–81. doi:10.1104/pp.107.106062. PMC   2151715 . PMID   17766396.
  81. Ruvkun G (October 2001). "Molecular biology. Glimpses of a tiny RNA world". Science. 294 (5543): 797–99. doi:10.1126/science.1066315. PMID   11679654. S2CID   83506718.
  82. Fichou Y, Férec C (December 2006). "The potential of oligonucleotides for therapeutic applications". Trends in Biotechnology. 24 (12): 563–70. doi:10.1016/j.tibtech.2006.10.003. PMID   17045686.
  83. Siebert S (2006). "Common sequence structure properties and stable regions in RNA secondary structures" (PDF). Dissertation, Albert-Ludwigs-Universität, Freiburg im Breisgau. p. 1. Archived from the original (PDF) on March 9, 2012.
  84. Szathmáry E (June 1999). "The origin of the genetic code: amino acids as cofactors in an RNA world". Trends in Genetics. 15 (6): 223–29. doi:10.1016/S0168-9525(99)01730-8. PMID   10354582.
  85. Jerome, Craig A.; et al. (19 May 2022). "Catalytic Synthesis of Polyribonucleic Acid on Prebiotic Rock Glasses". Astrobiology . 22 (6): 629–636. Bibcode:2022AsBio..22..629J. doi:10.1089/ast.2022.0027. PMC   9233534 . PMID   35588195. S2CID   248917871.
  86. Foundation for Applied Molecular Evolution (3 June 2022). "Scientists announce a breakthrough in determining life's origin on Earth—and maybe Mars". Phys.org . Retrieved 3 June 2022.
  87. Marlaire R (3 March 2015). "NASA Ames Reproduces the Building Blocks of Life in Laboratory". NASA . Retrieved 5 March 2015.
  88. Starr, Michelle (8 July 2022). "Loads of Precursors For RNA Have Been Detected in The Center of Our Galaxy". ScienceAlert . Retrieved 9 July 2022.
  89. Rivilla, Victor M.; et al. (8 July 2022). "Molecular Precursors of the RNA-World in Space: New Nitriles in the G+0.693−0.027 Molecular Cloud". Frontiers in Astronomy and Space Sciences . 9: 876870. arXiv: 2206.01053 . Bibcode:2022FrASS...9.6870R. doi: 10.3389/fspas.2022.876870 .