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

2017; National Academy of Sciences; Volume: 115; Issue: 2 Linguagem: Inglês

10.1073/pnas.1717794115

1091-6490

Chong Tang, Rachel Klukovich, Hongying Peng, Zhuqing Wang, Tian Yu, Ying Zhang, Huili Zheng, Arne Klungland, Wei Yan,

Cancer-related molecular mechanisms research

Significance N6-methyladnosine (m6A) represents one of the most common RNA modifications. Biochemical analyses have identified ALKBH5 as an eraser of m6A. The present study represents the first molecular characterization of the Alkbh5 knockout mouse model. Our data associate m6A erasure with mRNA length control. Specifically, proper m6A demethylation is required for correct splicing and selective degradation of longer 3′-UTR transcripts, which are abundant in mitotic and meiotic male germ cells, but these longer 3′-UTR transcripts become rapidly degraded in the haploid male germ cells. Aberrant m6A levels in spermatogenic cells are incompatible with normal spermatogenesis and male fertility.