ALKBH5-dependent m6A demethylation controls splicing and stability of long 3'-UTR mRNAs in male germ cells.

Abstract:

:N6-methyladenosine (m6A) represents one of the most common RNA modifications in eukaryotes. Specific m6A writer, eraser, and reader proteins have been identified. As an m6A eraser, ALKBH5 specifically removes m6A from target mRNAs and inactivation of Alkbh5 leads to male infertility in mice. However, the underlying molecular mechanism remains unknown. Here, we report that ALKBH5-mediated m6A erasure in the nuclei of spermatocytes and round spermatids is essential for correct splicing and the production of longer 3'-UTR mRNAs, and failure to do so leads to aberrant splicing and production of shorter transcripts with elevated levels of m6A that are rapidly degraded. Our study identified reversible m6A modification as a critical mechanism of posttranscriptional control of mRNA fate in late meiotic and haploid spermatogenic cells.

authors

Tang C,Klukovich R,Peng H,Wang Z,Yu T,Zhang Y,Zheng H,Klungland A,Yan W

doi

10.1073/pnas.1717794115

subject

Has Abstract

pub_date

2018-01-09 00:00:00

pages

E325-E333

issue

2

eissn

0027-8424

issn

1091-6490

pii

1717794115

journal_volume

115

pub_type

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