Cell
Volume 159, Issue 6, 4 December 2014, Pages 1365-1376
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Article
Uridylation by TUT4 and TUT7 Marks mRNA for Degradation

https://doi.org/10.1016/j.cell.2014.10.055Get rights and content
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Highlights

  • TUT4 and TUT7 uridylate mRNAs and thereby facilitate mRNA decay

  • TUT4 and TUT7 selectively uridylate deadenylated mRNAs with a short A-tail (<∼25 nt)

  • Uridylation is induced by miRNAs and enhances degradation of miRNA targets

  • Oligo-U-tail serves as a general molecular mark for mRNA decay

Summary

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.

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