Literature DB >> 25480299

Uridylation by TUT4 and TUT7 marks mRNA for degradation.

Jaechul Lim1, Minju Ha1, Hyeshik Chang1, S Chul Kwon1, Dhirendra K Simanshu2, Dinshaw J Patel2, V Narry Kim3.   

Abstract

Uridylation occurs pervasively on mRNAs, yet its mechanism and significance remain unknown. By applying TAIL-seq, we identify TUT4 and TUT7 (TUT4/7), also known as ZCCHC11 and ZCCHC6, respectively, as mRNA uridylation enzymes. Uridylation readily occurs on deadenylated mRNAs in cells. Consistently, purified TUT4/7 selectively recognize and uridylate RNAs with short A-tails (less than ∼ 25 nt) in vitro. PABPC1 antagonizes uridylation of polyadenylated mRNAs, contributing to the specificity for short A-tails. In cells depleted of TUT4/7, the vast majority of mRNAs lose the oligo-U-tails, and their half-lives are extended. Suppression of mRNA decay factors leads to the accumulation of oligo-uridylated mRNAs. In line with this, microRNA induces uridylation of its targets, and TUT4/7 are required for enhanced decay of microRNA targets. Our study explains the mechanism underlying selective uridylation of deadenylated mRNAs and demonstrates a fundamental role of oligo-U-tail as a molecular mark for global mRNA decay.
Copyright © 2014 Elsevier Inc. All rights reserved.

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Year:  2014        PMID: 25480299      PMCID: PMC4720960          DOI: 10.1016/j.cell.2014.10.055

Source DB:  PubMed          Journal:  Cell        ISSN: 0092-8674            Impact factor:   41.582


  51 in total

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  111 in total

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Review 10.  Controlling translation via modulation of tRNA levels.

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