2'-O-methylation explained

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. 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. 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

Notes and References

  1. Guo J . Transcription: the epicenter of gene expression . Journal of Zhejiang University. Science. B . 15 . 5 . 409–411 . May 2014 . 24793758 . 4076597 . 10.1631/jzus.B1400113 .
  2. Monaco PL, Marcel V, Diaz JJ, Catez F . 2'-O-Methylation of Ribosomal RNA: Towards an Epitranscriptomic Control of Translation? . Biomolecules . 8 . 4 . 106 . October 2018 . 30282949 . 6316387 . 10.3390/biom8040106 . free .
  3. Dimitrova DG, Teysset L, Carré C . RNA 2'-O-Methylation (Nm) Modification in Human Diseases . Genes . 10 . 2 . 117 . February 2019 . 30764532 . 6409641 . 10.3390/genes10020117 . free .
  4. Abou Assi H, Rangadurai AK, Shi H, Liu B, Clay MC, Erharter K, Kreutz C, Holley CL, Al-Hashimi HM . 2'-O-Methylation can increase the abundance and lifetime of alternative RNA conformational states . Nucleic Acids Research . 48 . 21 . 12365–12379 . December 2020 . 33104789 . 7708057 . 10.1093/nar/gkaa928 .
  5. Kiss T . Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs . The EMBO Journal . 20 . 14 . 3617–3622 . July 2001 . 11447102 . 125535 . 10.1093/emboj/20.14.3617 .
  6. Erales J, Marchand V, Panthu B, Gillot S, Belin S, Ghayad SE, Garcia M, Laforêts F, Marcel V, Baudin-Baillieu A, Bertin P, Couté Y, Adrait A, Meyer M, Therizols G, Yusupov M, Namy O, Ohlmann T, Motorin Y, Catez F, Diaz JJ . 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 . December 2017 . 29158377 . 5724255 . 10.1073/pnas.1707674114 . free . 2017PNAS..11412934E .
  7. Sun WJ, Li JH, Liu S, Wu J, Zhou H, Qu LH, Yang JH . RMBase: a resource for decoding the landscape of RNA modifications from high-throughput sequencing data . Nucleic Acids Research . 44 . D1 . D259–D265 . January 2016 . 26464443 . 4702777 . 10.1093/nar/gkv1036 .
  8. Marchand V, Blanloeil-Oillo F, Helm M, Motorin Y . Illumina-based RiboMethSeq approach for mapping of 2'-O-Me residues in RNA . Nucleic Acids Research . 44 . 16 . e135 . September 2016 . 27302133 . 5027498 . 10.1093/nar/gkw547 .
  9. Khoshnevis S, Dreggors-Walker RE, Marchand V, Motorin Y, Ghalei H . 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 . March 2022 . 35294285 . 8944910 . 10.1073/pnas.2117334119 . free . 2022PNAS..11917334K .
  10. Rana AK, Ankri S . Reviving the RNA World: An Insight into the Appearance of RNA Methyltransferases . Frontiers in Genetics . 7 . 99 . 2016 . 27375676 . 4893491 . 10.3389/fgene.2016.00099 . free .

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