2'-O-methylation

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]

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

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

• Nucleic acid analogue
• Small nucleolar RNA

References

1. 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. 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.