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2'-O-methylation
Biological molecule
Biological molecule
2'-O-methylation (2'-O-Me) is a nucleotide epitranscriptomics modification commonly found in ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA). This modification is created through post-transcriptional modification of the RNA. This modification can be performed via ribonucleoprotein (snoRNP) with C/D box small nucleolar RNA (snoRNA) used as a guide RNA where a methyl group is added to the 2' hydroxyl of the ribose moiety of any nucleotide (Nm) producing a methoxy group. It can also be performed through other enzymes without a guide RNA such as FTSJ1 in tRNAs. The modification of one Nm creates more stabilization in the structure by 0.2kcal/mol which is more enthalpically favorable. Currently, about 55 2'-O-methylations have been identified in yeast alone and 106 in humans and deposited in RNA Modification Base (RMBase) database.
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. 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.
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.
References
References
- Zhou, Katherine I.. (2024-05-01). "2′-O-methylation (Nm) in RNA: progress, challenges, and future directions". RNA.
- (May 2014). "Transcription: the epicenter of gene expression". Journal of Zhejiang University. Science. B.
- (October 2018). "2'-O-Methylation of Ribosomal RNA: Towards an Epitranscriptomic Control of Translation?". Biomolecules.
- (February 2019). "RNA 2'-O-Methylation (Nm) Modification in Human Diseases". Genes.
- (December 2020). "2'-O-Methylation can increase the abundance and lifetime of alternative RNA conformational states". Nucleic Acids Research.
- (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.
- (January 2016). "RMBase: a resource for decoding the landscape of RNA modifications from high-throughput sequencing data". Nucleic Acids Research.
- (September 2016). "Illumina-based RiboMethSeq approach for mapping of 2'-O-Me residues in RNA". Nucleic Acids Research.
- (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.
- (2016). "Reviving the RNA World: An Insight into the Appearance of RNA Methyltransferases". Frontiers in Genetics.
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