Regulatory RNA

RNA methylation recently found to be a widespread epigenetic modification

DNA methylation is one of the most important and most intensively studied areas of epigenetic regulation.  However, there is not much known about the methylation of RNA molecules and whether RNA methylation is an epigenetic mechanism to regulate gene expression or other cellular processes.  RNA can be methylated at the N6 position of adenosine (m6A), but the functional relevance of this post-transcriptional modification is not clear.

In a recent paper, Meyer et al. described a novel methylated RNA immunoprecipitation assay (specific for m6A) combined with next-generation sequencing (MeRIP-seq) and discovered that at least 7,676 mammalian mRNAs contain m6A modifications.  They found that transcripts were specifically enriched for m6A near the stop codon and in 3’ untranslated regions, and many m6A sites were in miRNA target sites.  m6A-modified mRNAs were identified in many different tissues, and the highest levels were found in the brain.  In addition to mRNAs, the m6A modification was also detected in non-coding RNAs.

This study establishes that RNA methylation is an abundant and dynamically regulated epigenetic phenomenon in mammalian cells.  RNA methylation is one of the most recently discovered epigenetic modifications, and this report suggests that it may have important regulatory functions for many RNAs.  More research is needed to determine the biological roles of methylated RNA, but possible activities of methylated RNA include regulating the secondary and higher order structure of RNA molecules, altering miRNA binding to transcripts, and acting as a binding site for RNA-binding proteins.  What else might methylated RNA be doing in cells?  Post your thoughts in the comments below.

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Meyer K.D., Saletore Y., Zumbo P., Elemento O., Mason C.E., and Jaffrey S.R.  (2012)

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Prediction of polyadenylation site usage from epigenetic modifications

Kevin B.

Kevin B.

Kevin grew up in Northern California and has also spent several years living on the East Coast. When he is not in the lab, Kevin enjoys snowboarding, watching NFL games (and playing fantasy football!), spending time outdoors, and exploring Southern California.

  • ZTariq

    Can addition of the 5′ cap to pre-mRNAs be considered epigenetic because technically it doesn’t alter the DNA sequence per se, but does impact gene expression? How about polyadenylation?

    • Thanks for the question! 5′ capping and polyadenylation are generally considered RNA processing events or post-transcriptional modifications, but you are right, they could also technically be referred to as epigenetic mechanisms.