2'-O-methylation

Last updated

2'-O-methyl-adenosine, a modified adenosine. 2'-O-Methyladenosine.svg
2'-O-methyl-adenosine, a modified adenosine.

2'-O-methylation (2'-O-Me) is a common nucleotide epitranscriptomics modification of ribosomal RNA (rRNA). The rRNA is transcribed from DNA and then used to create proteins through translation. [1] The resulting protein would normally be solely dependent on the gene it was translated from, but the methylation of the RNA would influence the outcome of the protein as well. [1] This modification to the rRNA is done via ribonucleoprotein (snoRNP) [2] where a methyl group is added to the 2' hydroxyl of the ribose moiety of any nucleotide (Nm) [3] producing a methoxy group. The modification of one Nm creates more stabilization in the structure by 0.2kcal/mol [4] which is more enthalpically favorable. 2'-O-methylated nucleotides are mostly found in post-translational ribosomal RNA and small nuclear RNA located in the ribosome and spliceosome. [5] Currently, about 55 2'-O-methylations have been identified in yeast alone and 106 in humans [6] and deposited in RNA Modification Base (RMBase) database. [7]

This modification is able to stabilize the structure of RNA while preventing it from undergoing hydrolysis as the hydroxyl group is replaced. [2] A technique was developed based on this property called RiboMethSeq to quantify the amount of modifications existing in a sample of rRNA. [8] RNA is a short lived molecule and each of the types vary in its longevity in the cell. Ribosomal RNA exists longer in the cell before degradation so utilizing 2'-O-Met would aid in stabilizing its structure. The epitranscriptomics of this particular RNA modification occurs post-translation, causing a change in the resulting protein without the DNA being altered. [9]

Having chemical properties intermediate between RNA and DNA, 2'-O-methylation is presumed to have been one of the reactive group of RNA molecules on early Earth that would have given rise to DNA. [10]

See also

Related Research Articles

<span class="mw-page-title-main">RNA</span> Family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

<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, though this ratio differs between prokaryotes and eukaryotes.

<span class="mw-page-title-main">RNA editing</span> Molecular process

RNA editing is a molecular process through which some cells can make discrete changes to specific nucleotide sequences within an RNA molecule after it has been generated by RNA polymerase. It occurs in all living organisms and is one of the most evolutionarily conserved properties of RNAs. RNA editing may include the insertion, deletion, and base substitution of nucleotides within the RNA molecule. RNA editing is relatively rare, with common forms of RNA processing not usually considered as editing. It can affect the activity, localization as well as stability of RNAs, and has been linked with human diseases.

<span class="mw-page-title-main">Post-transcriptional modification</span> RNA processing within a biological cell

Transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature, functional RNA molecule that can then leave the nucleus and perform any of a variety of different functions in the cell. There are many types of post-transcriptional modifications achieved through a diverse class of molecular mechanisms.

<span class="mw-page-title-main">Small nucleolar RNA SNORD102</span>

In molecular biology, snoRNA U102 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD18</span>

In molecular biology, SNORD18 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD34</span>

In molecular biology, snoRNA U34 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD35</span>

In molecular biology, snoRNA U35 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD43</span>

In molecular biology, snoRNA U43 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD46</span>

In molecular biology, snoRNA U46 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD62</span>

In molecular biology, snoRNA U62 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA TBR7</span>

In molecular biology, Small nucleolar RNA TBR7 is a non-coding RNA (ncRNA) molecule identified in Trypanosoma brucei which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD88</span>

In molecular biology, Small Nucleolar RNA SNORD88 is a non-coding RNA (ncRNA) molecule which functions in the biogenesis (modification) of other small nuclear RNAs (snRNAs). This type of modifying RNA is located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

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.

<span class="mw-page-title-main">60S ribosomal protein L7</span> Protein found in humans

60S ribosomal protein L7 is a protein that in humans is encoded by the RPL7 gene.

<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 heterochromatin, therefore exhibiting a type of quaternary structure, gene transcription will be inhibited.

Ribosome profiling, or Ribo-Seq, is an adaptation of a technique developed by Joan Steitz and Marilyn Kozak almost 50 years ago that Nicholas Ingolia and Jonathan Weissman adapted to work with next generation sequencing that uses specialized messenger RNA (mRNA) sequencing to determine which mRNAs are being actively translated. A related technique that can also be used to determine which mRNAs are being actively translated is the Translating Ribosome Affinity Purification (TRAP) methodology, which was developed by Nathaniel Heintz at Rockefeller University. TRAP does not involve ribosome footprinting but provides cell type-specific information.

RRNA small subunit pseudouridine methyltransferase Nep1 (EC 2.1.1.260, Nep1, nucleolar essential protein 1) is an enzyme with systematic name S-adenosyl-L-methionine:18S rRNA (pseudouridine1191-N1)-methyltransferase. This enzyme catalyses the following chemical reaction

Within the field of molecular biology, the epitranscriptome includes all the biochemical modifications of the RNA within a cell. In analogy to epigenetics that describes "functionally relevant changes to the genome that do not involve a change in the nucleotide sequence", epitranscriptomics involves all functionally relevant changes to the transcriptome that do not involve a change in the ribonucleotide sequence. Thus, the epitranscriptome can be defined as the ensemble of such functionally relevant changes.

RNA Modification Base (RMBase) is designed for decoding the landscape of RNA modifications identified from high-throughput sequencing data. It contains ~124200 N6-Methyladenosines (m6A), ~9500 pseudouridine (Ψ) modifications, ~1000 5-methylcytosine (m5C) modifications, ~1210 2′-O-methylations (2′-O-Me) and ~3130 other types of RNA modifications. RMBase demonstrated thousands of RNA modifications located within mRNAs, regulatory ncRNAs, miRNA target sites and disease-related SNPs.

References

  1. 1 2 Guo J (May 2014). "Transcription: the epicenter of gene expression". Journal of Zhejiang University. Science. B. 15 (5): 409–411. doi:10.1631/jzus.B1400113. PMC   4076597 . PMID   24793758.
  2. 1 2 Monaco PL, Marcel V, Diaz JJ, Catez F (October 2018). "2'-O-Methylation of Ribosomal RNA: Towards an Epitranscriptomic Control of Translation?". Biomolecules. 8 (4): 106. doi: 10.3390/biom8040106 . PMC   6316387 . PMID   30282949.
  3. ↑ Dimitrova DG, Teysset L, Carré C (February 2019). "RNA 2'-O-Methylation (Nm) Modification in Human Diseases". Genes. 10 (2): 117. doi: 10.3390/genes10020117 . PMC   6409641 . PMID   30764532.
  4. ↑ Abou Assi H, Rangadurai AK, Shi H, Liu B, Clay MC, Erharter K, et al. (December 2020). "2'-O-Methylation can increase the abundance and lifetime of alternative RNA conformational states". Nucleic Acids Research. 48 (21): 12365–12379. doi:10.1093/nar/gkaa928. PMC   7708057 . PMID   33104789.
  5. ↑ Kiss T (July 2001). "Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs". The EMBO Journal. 20 (14): 3617–3622. doi:10.1093/emboj/20.14.3617. PMC   125535 . PMID   11447102.
  6. ↑ Erales J, Marchand V, Panthu B, Gillot S, Belin S, Ghayad SE, et al. (December 2017). "Evidence for rRNA 2'-O-methylation plasticity: Control of intrinsic translational capabilities of human ribosomes". Proceedings of the National Academy of Sciences of the United States of America. 114 (49): 12934–12939. Bibcode:2017PNAS..11412934E. doi: 10.1073/pnas.1707674114 . PMC   5724255 . PMID   29158377.
  7. ↑ Sun WJ, Li JH, Liu S, Wu J, Zhou H, Qu LH, et al. (January 2016). "RMBase: a resource for decoding the landscape of RNA modifications from high-throughput sequencing data". Nucleic Acids Research. 44 (D1): D259–D265. doi:10.1093/nar/gkv1036. PMC   4702777 . PMID   26464443.
  8. ↑ Marchand V, Blanloeil-Oillo F, Helm M, Motorin Y (September 2016). "Illumina-based RiboMethSeq approach for mapping of 2'-O-Me residues in RNA". Nucleic Acids Research. 44 (16): e135. doi:10.1093/nar/gkw547. PMC   5027498 . PMID   27302133.
  9. ↑ Khoshnevis S, Dreggors-Walker RE, Marchand V, Motorin Y, Ghalei H (March 2022). "Ribosomal RNA 2'-O-methylations regulate translation by impacting ribosome dynamics". Proceedings of the National Academy of Sciences of the United States of America. 119 (12): e2117334119. Bibcode:2022PNAS..11917334K. doi: 10.1073/pnas.2117334119 . PMC   8944910 . PMID   35294285.
  10. ↑ Rana AK, Ankri S (2016). "Reviving the RNA World: An Insight into the Appearance of RNA Methyltransferases". Frontiers in Genetics. 7: 99. doi: 10.3389/fgene.2016.00099 . PMC   4893491 . PMID   27375676.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.