Uridylation by TUT4 and TUT7 marks mRNA for degradation Journal Article
| Authors: | Lim, J.; Ha, M.; Chang, H.; Kwon, S. C.; Simanshu, D. K.; Patel, D. J.; Kim, V. N. |
| Article Title: | Uridylation by TUT4 and TUT7 marks mRNA for degradation |
| 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 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. |
| Keywords: | proteins; microrna; quality-control; translational repression; decay; lin28-let-7 pathway; cytoplasmic rna; poly(a) tail; stem-loop; 3' end |
| Journal Title: | Cell |
| Volume: | 159 |
| Issue: | 6 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2014-12-04 |
| Start Page: | 1365 |
| End Page: | 1376 |
| Language: | English |
| ACCESSION: | WOS:000346652900015 |
| DOI: | 10.1016/j.cell.2014.10.055 |
| PROVIDER: | wos |
| PUBMED: | 25480299 |
| PMCID: | PMC4720960 |
| Notes: | Article -- Source: Wos |
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