Terminal Uridylyltransferases Execute Programmed Clearance of Maternal Transcriptome in Vertebrate Embryos

Terminal Uridylyltransferases Execute Programmed Clearance of Maternal Transcriptome in Vertebrate Embryos
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DOI:
10.1016/j.molcel.2018.03.004
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发表时间:
2018-04-05
期刊:
影响因子:
16
通讯作者:
Kim, V. Narry
Kim, V. Narry
中科院分区:
生物学1区
文献类型:
--
作者:
Chang, Hyeshik;Yeo, Jinah;Kim, V. Narry

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在母体-合子转化(MZT)过程中,母体rna被主动降解并被新合成的合子转录物以高度协调的方式取代。然而,在早期脊椎动物胚胎中母体mRNA衰变是如何触发的,这在很大程度上仍然是未知的。在这里,通过RNA丰度和30修饰的全基因组分析,我们发现尿苷化是在母体mRNA清除开始时诱导的。尿苷化的时间控制在脊椎动物中是保守的。当末端尿苷基转移酶TUT4和TUT7 (TUT4/7)的同源物在斑马鱼和非洲爪鱼中缺失时,母体mRNA的清除明显延迟,导致原肠胚发育缺陷。短尾mrna被TUT4/7选择性地尿苷化,在MZT期间,高度尿苷化的转录物比那些未修饰的聚(A)尾部的转录物降解得更快。我们的研究表明尿苷化在及时的mRNA降解中起着至关重要的作用,从而允许早期发育的进展。
During the maternal-to-zygotic transition (MZT), maternal RNAs are actively degraded and replaced by newly synthesized zygotic transcripts in a highly coordinated manner. However, it remains largely unknown how maternal mRNA decay is triggered in early vertebrate embryos. Here, through genome-wide profiling of RNA abundance and 30 modification, we show that uridylation is induced at the onset of maternal mRNA clearance. The temporal control of uridylation is conserved in vertebrates. When the homologs of terminal uridylyltransferases TUT4 and TUT7 (TUT4/7) are depleted in zebrafish and Xenopus, maternal mRNA clearance is significantly delayed, leading to developmental defects during gastrulation. Short-tailed mRNAs are selectively uridylated by TUT4/7, with the highly uridylated transcripts degraded faster during the MZT than those with unmodified poly(A) tails. Our study demonstrates that uridylation plays a crucial role in timely mRNA degradation, thereby allowing the progression of early development.