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信使核糖核酸3'端尿苷酸化和聚腺苷酸尾长度塑造哺乳动物母体转录组。

mRNA 3' uridylation and poly(A) tail length sculpt the mammalian maternal transcriptome.

作者信息

Morgan Marcos, Much Christian, DiGiacomo Monica, Azzi Chiara, Ivanova Ivayla, Vitsios Dimitrios M, Pistolic Jelena, Collier Paul, Moreira Pedro N, Benes Vladimir, Enright Anton J, O'Carroll Dónal

机构信息

MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH16 4UU, UK.

European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo 00015, Italy.

出版信息

Nature. 2017 Aug 17;548(7667):347-351. doi: 10.1038/nature23318. Epub 2017 Aug 9.

Abstract

A fundamental principle in biology is that the program for early development is established during oogenesis in the form of the maternal transcriptome. How the maternal transcriptome acquires the appropriate content and dosage of transcripts is not fully understood. Here we show that 3' terminal uridylation of mRNA mediated by TUT4 and TUT7 sculpts the mouse maternal transcriptome by eliminating transcripts during oocyte growth. Uridylation mediated by TUT4 and TUT7 is essential for both oocyte maturation and fertility. In comparison to somatic cells, the oocyte transcriptome has a shorter poly(A) tail and a higher relative proportion of terminal oligo-uridylation. Deletion of TUT4 and TUT7 leads to the accumulation of a cohort of transcripts with a high frequency of very short poly(A) tails, and a loss of 3' oligo-uridylation. By contrast, deficiency of TUT4 and TUT7 does not alter gene expression in a variety of somatic cells. In summary, we show that poly(A) tail length and 3' terminal uridylation have essential and specific functions in shaping a functional maternal transcriptome.

摘要

生物学中的一个基本原则是,早期发育程序是以母体转录组的形式在卵子发生过程中建立的。母体转录组如何获得适当的转录本内容和剂量尚不完全清楚。在这里,我们表明,由TUT4和TUT7介导的mRNA的3'末端尿苷酸化通过在卵母细胞生长过程中消除转录本来塑造小鼠母体转录组。由TUT4和TUT7介导的尿苷酸化对于卵母细胞成熟和生育能力都是必不可少的。与体细胞相比,卵母细胞转录组具有较短的聚腺苷酸尾巴和较高的末端寡聚尿苷酸化相对比例。TUT4和TUT7的缺失导致一批具有非常短的聚腺苷酸尾巴高频的转录本积累,以及3'寡聚尿苷酸化的丧失。相比之下,TUT4和TUT7的缺陷不会改变多种体细胞中的基因表达。总之,我们表明聚腺苷酸尾巴长度和3'末端尿苷酸化在塑造功能性母体转录组中具有重要且特定的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65fa/5768236/8dc67de5c9bf/emss-73169-f005.jpg

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