Nascent RNA m6A modification at the heart of the gene–retrotransposon conflict

Abstract

Retrotransposons are highly abundant mobile genetic elements in mammalian genomes and can interfere with many genomic processes, particularly the transcription of genes. A study by Xiong et al. reveals that segments of nascent RNAs containing retrotransposons are enriched in N 6 -methyladenosine and act as transcriptional roadblocks for elongating RNA polymerase II, but that cellular proteins capable of binding to these RNAs, SAFB/SAFB2, can mitigate this effect.Long interspersed element 1 (L1) retrotransposons are transposable elements capable of propagating within genomes by a copy-and-paste mechanism through an RNA intermediate and a reverse transcription step. They are present in many eukaryotic lineages, but have been, and still are, particularly active in mammals, acting as potent endogenous mutagens. They are strongly silenced by several layers of transcriptional and posttranscriptional mechanisms, both in the nucleus and in the

An update on post‐transcriptional regulation of retrotransposons

“…This was antagonized by SAFB and SAFB2 proteins, which showed preferential binding to m 6 A-modified LINE-1 RNA, leading to their increased degradation and in effect reduced retrotransposition. However, the major finding of the study is likely the identification of m 6 Arich intronic L1s, called MILs, which following [111,112]. Results of another study in human cells also confirm the close interplay between m 6 A and LINE-1 but present a different regulatory mechanism that operates specifically during the S and G2/M phases of the cell cycle [113].…”

“…However, the major finding of the study is likely the identification of m 6 A‐rich intronic L1s, called MILs, which following transcription are enriched for m 6 A, leading to MIL and m 6 A‐dependent attenuation of transcription downstream of the MIL. Thus, Xiong et al., by identifying MILs, demonstrated a novel LINE‐1‐mediated regulatory mechanism of transcription of other genes curiously including some DNA repair factors demonstrated to affect LINE‐1s and generally long genes enriched in those involved in neuronal/synaptic functions [111,112]. Results of another study in human cells also confirm the close interplay between m 6 A and LINE‐1 but present a different regulatory mechanism that operates specifically during the S and G2/M phases of the cell cycle [113].…”