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10.1016/j.molcel.2014.07.017

http://scihub22266oqcxt.onion/10.1016/j.molcel.2014.07.017
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suck abstract from ncbi


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pmid25175028      Mol+Cell 2014 ; 55 (6): 868-79
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  • A MicroRNA Precursor Surveillance System in Quality Control of MicroRNA Synthesis #MMPMID25175028
  • Liu X; Zheng Q; Vrettos N; Maragkakis M; Alexiou P; Gregory BD; Mourelatos Z
  • Mol Cell 2014[Sep]; 55 (6): 868-79 PMID25175028show ga
  • MicroRNAs (miRNAs) are essential for regulation of gene expression. Though numerous miRNAs have been identified by high throughput sequencing, few precursor miRNAs (pre-miRNAs) are experimentally validated. Here we report a strategy for constructing high-throughput sequencing libraries enriched for full-length pre-miRNAs. We find widespread and extensive uridylation of Argonaute bound pre-miRNAs, which is primarily catalyzed by two terminal uridylyltransferases: TUT7 and TUT4. Uridylation by TUT7/4 not only polishes pre-miRNA 3? ends, but also facilitates their degradation by the exosome, preventing clogging of Ago with defective species. We show that the exosome exploits distinct substrate preferences of DIS3 and RRP6, its two catalytic subunits, to distinguish productive from defective pre-miRNAs. Furthermore, we identify a positive feedback loop formed by the exosome and TUT7/4 in triggering uridylation and degradation of Ago-bound pre-miRNAs. Our study reveals a pre-miRNA surveillance system that comprises TUT7, TUT4 and the exosome in quality control of miRNA synthesis.
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