S-Space College of Natural Sciences (자연과학대학) Dept. of Biological Sciences (생명과학부) Journal Papers (저널논문_생명과학부)
Uridylation by TUT4 and TUT7 marks mRNA for degradation
- Lim, Jaechul; Ha, Minju; Chang, Hyeshik; Kwon, S. Chul; Simanshu, Dhirendra K.; Patel, Dinshaw J.; Kim, V. Narry
- Issue Date
- Cell, Vol.159 No.6, pp.1365-1376
- 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 similar to 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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