2'-O-methylation

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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

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<span class="mw-page-title-main">Small nucleolar RNA SNORD83</span>

In molecular biology, Small nucleolar RNA SNORD83 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. snoRNA SNORD83 belongs to the C/D box class of snoRNAs which contain the conserved sequence motifs known as the C box (UGAUGA) and the D box (CUGA). Most of the members of the box C/D family function in directing site-specific 2'-O-methylation of substrate RNAs. snoRNA SNORD83 are spliced from introns 5 and 4 of the BAT1 gene in mammals.

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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.
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