文章基本信息

标题：ALKBH5-dependent m6A demethylation controls splicing and stability of long 3′-UTR mRNAs in male germ cells
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作者：Chong Tang ; Rachel Klukovich ; Hongying Peng 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：2
页码：E325-E333
DOI：10.1073/pnas.1717794115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：RNA methylation ; alternative splicing ; mRNA stability ; 3′-UTR shortening ; fertility