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Comment
. 2017 May 15;31(10):957-958.
doi: 10.1101/gad.302695.117.

Settling the m6A debate: methylation of mature mRNA is not dynamic but accelerates turnover

Nicolle A Rosa-Mercado  1 , Johanna B Withers  1 , Joan A Steitz  1   2
Affiliations
Comment

Settling the m6A debate: methylation of mature mRNA is not dynamic but accelerates turnover

Nicolle A Rosa-Mercado et al. Genes Dev. .

Abstract

Post-transcriptional modification of RNA nucleosides has been implicated as a pivotal regulator of mRNA biology. In this issue of Genes & Development, Ke and colleagues (pp. 990-1006) provide insights into the temporal and spatial distribution of N6-methyladenosine (m6A) in RNA transcripts by analyzing different subcellular fractions. Using a recently developed biochemical approach for detecting m6A, the researchers show that m6A methylations are enriched in exons and are added to transcripts prior to splicing. Although m6A addition is widely thought to be readily reversible, they demonstrate in HeLa cells that once RNA is released from chromatin, the modifications are surprisingly static. This study integrates data from previous publications to clarify conflicting conclusions regarding the role of m6A in mRNA biogenesis and function. Ke and colleagues found that m6A methylation levels negatively correlate with transcript half-life but are not required for most pre-mRNA splicing events.

Keywords: cell fractionation; m6A-CLIP; mRNA turnover; pre-mRNA.

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Figures

Figure 1.
Figure 1.
m6A modifications are added to exonic sequences before splicing and shorten mRNA half-life. RNA polymerase II (blue) synthesizes the pre-mRNA transcript, and, prior to the completion of splicing, a methylation complex containing METTL3 selectively adds m6A modifications to exonic sequences (thicker black bars). After release of spliced mRNA first into the nucleoplasm and ultimately into the cytoplasm, no further additions or subtractions of m6A are detected. The presence of m6A in an mRNA accelerates turnover.
See this image and copyright information in PMC

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References

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