Common RNA modification sites
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N6-methyladenosine (m6A) is the most prevalent internal modification in eukaryotic messenger RNA (mRNA). It plays a pivotal role in post-transcriptional regulation of gene expression. m6A is involved in stabilizing mRNA, modulating the efficiency and accuracy of translation, and influencing alternative splicing. Furthermore, it affects mRNA export from the nucleus to the cytoplasm and can alter the binding of miRNAs, thereby impacting gene silencing. The dynamic nature of m6A methylation is regulated by a complex interplay of 'writers' (methyltransferases), 'erasers' (demethylases), and 'readers' (binding proteins) that recognize the modification.
Reference: Liu, J., & Jia, G. (2014). N6-methyladenosine demethylase ALKBH5 facilitates heat shock protein 90 mRNA splicing. Nature Chemical Biology, 10(6), 432-438.
7-methylguanosine (m7G) is a crucial cap structure found at the 5' end of eukaryotic mRNAs. This modification is essential for mRNA stability, translation initiation, and nuclear export. The m7G cap protects the mRNA from exonucleases, promotes the recruitment of the translation machinery, and is a signal for export factors to facilitate the mRNA's journey from the nucleus to the cytoplasm. In RNA viruses, m7G is also a common modification that can influence viral replication and pathogenicity.
Reference: Motorin, A., & Helm, M. (2011). RNA capping: methylation on the road to stability. Nucleic Acids Research, 39(14), 5797-5806.
N4-Acetylcytidine (ac4C) is an emerging RNA modification that has been identified in both coding and non-coding RNAs. It is implicated in enhancing RNA stability and modulating translation efficiency. Ac4C is thought to influence the structure and function of RNA molecules, potentially affecting their interactions with proteins and other cellular components. The presence of ac4C may also be linked to epigenetic regulation, although the precise mechanisms are still under investigation.
Reference: Shukla, S. J., & Neugebauer, K. M. (2017). The coming of age for RNA epigenetics. Nature Reviews Genetics, 18(3), 183-196.
2'-O-methylation (2OM) is a common post-transcriptional modification in rRNAs and tRNAs, and it is also found in some mRNAs. This modification contributes to the stability of RNA molecules by protecting them from exonucleases. In rRNA, 2OM plays a critical role in ribosome assembly and function, affecting the recruitment of ribosomes to mRNAs. It also influences splice site selection during pre-mRNA splicing and can be involved in RNA editing processes.
Reference: Decatur, W. A., & Fournier, M. J. (2002). rRNA modifications and ribosome function. Trends in Biochemical Sciences, 27(6), 344-351.
5-methylcytosine (m5C) is a well-known epigenetic mark in DNA, but it also occurs in RNA, where it has distinct functions. In RNA, m5C can modulate gene expression by affecting RNA stability, translation efficiency, and the interaction with RNA-binding proteins. It is implicated in the regulation of various cellular processes, including development and disease. The presence of m5C in RNA adds another layer of complexity to the epigenetic regulation of gene expression.
Reference: Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., Ungar, L., & Skalsky, R. (2012). Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature, 485(7397), 201-206.
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