Pre-mRNA processing includes N⁶ methylation of adenosine residues that are retained in mRNA exons and the fallacy of “RNA epigenetics”

Abstract

By using a cell fraction technique that separates chromatin associated nascent RNA, newly completed nucleoplasmic mRNA and cytoplasmic mRNA, we have shown (Ke et al. 2017) that residues in exons are methylated (m 6 A) in nascent pre-mRNA and remain methylated in the same exonic residues in nucleoplasmic and cytoplasmic mRNA. Thus, there is no evidence of a substantial degree of demethylation in mRNA exons that would correspond to so-called "epigenetic" demethylation. The turnover rate of mRNA molecules is faster depending on m 6 A content in HeLa cell mRNA suggesting specification of mRNA stability may be the major role of

FTO, m6Am, and the hypothesis of reversible epitranscriptomic mRNA modifications

“…These authors concluded that once m 6 A is formed, it is not subsequently removed. Their reanalysis nearly 35 years after their initial study came to the same conclusion [44]. Their reanalysis nearly 35 years after their initial study came to the same conclusion [44].…”

“…Darnell and colleagues replicated this finding more recently using more sensitive m 6 A-detection methods and m 6 A mapping techniques [43]. Their reanalysis nearly 35 years after their initial study came to the same conclusion [44]. It should be noted that their inability to detect m 6 A loss from mRNA does not exclude the possibility that m 6 A demethylation is elicited by some type of signal that was not used in their assays.…”

The role of RNA modifications in the regulation of tRNA cleavage

“…Despite the recent fervor and debate surrounding the role of RNA modifications in mRNA , the presence of a multitude of modifications has long been known in tRNA. Early enzymatic digests of calf liver RNA showed mononucleotides that did not correspond to the four canonical RNA bases .…”

Adenosine methylation as a molecular imprint defining the fate of RNA

“…levels remaining unchanged in the three cellular compartments studied and by extension proposed that quantitatively little methylation or demethylation occurs on cytoplasmic mRNA. This view is at odds with the idea of m 6 A being a dynamic modification and is currently a matter of debate [16][17][18].…”