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The S. cerevisiae m6A-reader Pho92 promotes timely meiotic recombination by controlling key methylated transcripts
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2022-08-08 , DOI: 10.1093/nar/gkac640
Jérémy Scutenaire 1, 2, 3, 4 , Damien Plassard 1, 2, 3, 4 , Mélody Matelot 1, 2, 3, 4 , Tommaso Villa 5 , Julie Zumsteg 6 , Domenico Libri 5 , Bertrand Séraphin 1, 2, 3, 4
Affiliation  

N6-Methyladenosine (m6A), one of the most abundant internal modification of eukaryotic mRNAs, participates in the post-transcriptional control of gene expression through recruitment of specific m6A readers. In Saccharomyces cerevisiae, the m6A methyltransferase Ime4 is expressed only during meiosis and its deletion impairs this process. To elucidate how m6A control gene expression, we investigated the function of the budding yeast m6A reader Pho92. We show that Pho92 is an early meiotic factor that promotes timely meiotic progression. High-throughput RNA sequencing and mapping of Pho92-binding sites following UV-crosslinking reveal that Pho92 is recruited to specific mRNAs in an m6A-dependent manner during the meiotic prophase, preceding their down-regulation. Strikingly, point mutations altering m6A sites in mRNAs targeted by Pho92 are sufficient to delay their down-regulation and, in one case, to slow down meiotic progression. Altogether, our results indicate that Pho92 facilitate the meiotic progression by accelerating the down-regulation of timely-regulated mRNAs during meiotic recombination.

中文翻译:

S. cerevisiae m6A-reader Pho92 通过控制关键的甲基化转录本促进适时的减数分裂重组

N6-甲基腺苷 (m6A) 是真核生物 mRNA 最丰富的内部修饰之一,通过招募特定的 m6A 阅读器参与基因表达的转录后控制。在酿酒酵母中,m6A 甲基转移酶 Ime4 仅在减数分裂期间表达,其缺失会损害该过程。为了阐明 m6A 如何控制基因表达,我们研究了出芽酵母 m6A 阅读器 Pho92 的功能。我们表明 Pho92 是促进减数分裂及时进展的早期减数分裂因子。UV 交联后 Pho92 结合位点的高通量 RNA 测序和作图表明,在减数分裂前期,Pho92 在其下调之前以 m6A 依赖性方式被招募到特定的 mRNA。引人注目的是,改变 Pho92 靶向的 mRNA 中 m6A 位点的点突变足以延迟它们的下调,并且在一种情况下,可以减缓减数分裂进程。总而言之,我们的结果表明 Pho92 通过在减数分裂重组期间加速及时调节的 mRNA 的下调来促进减数分裂进程。
更新日期:2022-08-08
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