DNA ligase is a type of enzyme that facilitates the joining of DNA strands together by catalyzing the formation of a phosphodiester bond. It plays a role in repairing single-strand breaks in duplex DNA in living organisms, but some forms may specifically repair double-strand breaks. Single-strand breaks are repaired by DNA ligase using the complementary strand of the double helix as a template, with DNA ligase creating the final phosphodiester bond to fully repair the DNA.
A polymerase is an enzyme that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base-pairing interactions or RNA by half ladder replication.
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.
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.
Deoxyribozymes, also called DNA enzymes, DNAzymes, or catalytic DNA, are DNA oligonucleotides that are capable of performing a specific chemical reaction, often but not always catalytic. This is similar to the action of other biological enzymes, such as proteins or ribozymes . However, in contrast to the abundance of protein enzymes in biological systems and the discovery of biological ribozymes in the 1980s, there is only little evidence for naturally occurring deoxyribozymes. Deoxyribozymes should not be confused with DNA aptamers which are oligonucleotides that selectively bind a target ligand, but do not catalyze a subsequent chemical reaction.
A nick is a discontinuity in a double stranded DNA molecule where there is no phosphodiester bond between adjacent nucleotides of one strand typically through damage or enzyme action. Nicks allow DNA strands to untwist during replication, and are also thought to play a role in the DNA mismatch repair mechanisms that fix errors on both the leading and lagging daughter strands.
Threose nucleic acid (TNA) is an artificial genetic polymer in which the natural five-carbon ribose sugar found in RNA has been replaced by an unnatural four-carbon threose sugar. Invented by Albert Eschenmoser as part of his quest to explore the chemical etiology of RNA, TNA has become an important synthetic genetic polymer (XNA) due to its ability to efficiently base pair with complementary sequences of DNA and RNA. However, unlike DNA and RNA, TNA is completely refractory to nuclease digestion, making it a promising nucleic acid analog for therapeutic and diagnostic applications.
The hammerhead ribozyme is an RNA motif that catalyzes reversible cleavage and ligation reactions at a specific site within an RNA molecule. It is one of several catalytic RNAs (ribozymes) known to occur in nature. It serves as a model system for research on the structure and properties of RNA, and is used for targeted RNA cleavage experiments, some with proposed therapeutic applications. Named for the resemblance of early secondary structure diagrams to a hammerhead shark, hammerhead ribozymes were originally discovered in two classes of plant virus-like RNAs: satellite RNAs and viroids. They are also known in some classes of retrotransposons, including the retrozymes. The hammerhead ribozyme motif has been ubiquitously reported in lineages across the tree of life.
The hairpin ribozyme is a small section of RNA that can act as a ribozyme. Like the hammerhead ribozyme it is found in RNA satellites of plant viruses. It was first identified in the minus strand of the tobacco ringspot virus (TRSV) satellite RNA where it catalyzes self-cleavage and joining (ligation) reactions to process the products of rolling circle virus replication into linear and circular satellite RNA molecules. The hairpin ribozyme is similar to the hammerhead ribozyme in that it does not require a metal ion for the reaction.
Leadzyme is a small ribozyme (catalytic RNA), which catalyzes the cleavage of a specific phosphodiester bond. It was discovered using an in-vitro evolution study where the researchers were selecting for RNAs that specifically cleaved themselves in the presence of lead. However, since then, it has been discovered in several natural systems. Leadzyme was found to be efficient and dynamic in the presence of micromolar concentrations of lead ions. Unlike in other small self-cleaving ribozymes, other divalent metal ions cannot replace Pb2+ in the leadzyme. Due to obligatory requirement for a lead, the ribozyme is called a metalloribozyme.
Group I introns are large self-splicing ribozymes. They catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. The core secondary structure consists of nine paired regions (P1-P9). These fold to essentially two domains – the P4-P6 domain and the P3-P9 domain. The secondary structure mark-up for this family represents only this conserved core. Group I introns often have long open reading frames inserted in loop regions.
The hepatitis delta virus (HDV) ribozyme is a non-coding RNA found in the hepatitis delta virus that is necessary for viral replication and is the only known human virus that utilizes ribozyme activity to infect its host. The ribozyme acts to process the RNA transcripts to unit lengths in a self-cleavage reaction during replication of the hepatitis delta virus, which is thought to propagate by a double rolling circle mechanism. The ribozyme is active in vivo in the absence of any protein factors and was the fastest known naturally occurring self-cleaving RNA at the time of its discovery.
In vitro compartmentalization (IVC) is an emulsion-based technology that generates cell-like compartments in vitro. These compartments are designed such that each contains no more than one gene. When the gene is transcribed and/or translated, its products become 'trapped' with the encoding gene inside the compartment. By coupling the genotype (DNA) and phenotype, compartmentalization allows the selection and evolution of phenotype.
The Lariat capping ribozyme is a ~180 nt ribozyme with an apparent resemblance to a group I ribozyme. It is found within a complex type of group I introns also termed twin-ribozyme introns. Rather than splicing, it catalyses a branching reaction in which the 2'OH of an internal residue is involved in a nucleophilic attack at a nearby phosphodiester bond. As a result, the RNA is cleaved at an internal processing site (IPS), leaving a 3'OH and a downstream product with a 3 nt lariat at its 5' end. The lariat has the first and the third nucleotide joined by a 2',5' phosphodiester bond and is referred to as 'the lariat cap' because it caps an intron-encoded mRNA. The resulting lariat cap seems to contribute by increasing the half-life of the HE mRNA, thus conferring an evolutionary advantage to the HE.
In chemistry, a hypercycle is an abstract model of organization of self-replicating molecules connected in a cyclic, autocatalytic manner. It was introduced in an ordinary differential equation (ODE) form by the Nobel Prize in Chemistry winner Manfred Eigen in 1971 and subsequently further extended in collaboration with Peter Schuster. It was proposed as a solution to the error threshold problem encountered during modelling of replicative molecules that hypothetically existed on the primordial Earth. As such, it explained how life on Earth could have begun using only relatively short genetic sequences, which in theory were too short to store all essential information. The hypercycle is a special case of the replicator equation. The most important properties of hypercycles are autocatalytic growth competition between cycles, once-for-ever selective behaviour, utilization of small selective advantage, rapid evolvability, increased information capacity, and selection against parasitic branches.
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.
Xeno nucleic acids (XNA) are synthetic nucleic acid analogues that have a different sugar backbone than the natural nucleic acids DNA and RNA. As of 2011, at least six types of synthetic sugars have been shown to form nucleic acid backbones that can store and retrieve genetic information. Research is now being done to create synthetic polymerases to transform XNA. The study of its production and application has created a field known as xenobiology.
The twister sister ribozyme (TS) is an RNA structure that catalyzes its own cleavage at a specific site. In other words, it is a self-cleaving ribozyme. The twister sister ribozyme was discovered by a bioinformatics strategy as an RNA Associated with Genes Associated with Twister and Hammerhead ribozymes, or RAGATH.
Background: The hatchet ribozyme is an RNA structure that catalyzes its own cleavage at a specific site. In other words, it is a self-cleaving ribozyme. Hatchet ribozymes were discovered by a bioinformatics strategy as RNAs Associated with Genes Associated with Twister and Hammerhead ribozymes, or RAGATH.
Philipp Holliger, Ph.D. is a Swiss molecular biologist best known for his work on xeno nucleic acids (XNAs) and RNA engineering. Holliger is a program leader at the MRC Laboratory of Molecular Biology.
