Uridylation by TUT4 and TUT7 marks mRNA for degradation

Cell. 2014 Dec 4;159(6):1365-76. doi: 10.1016/j.cell.2014.10.055.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Humans
  • MicroRNAs / metabolism
  • Poly A / metabolism
  • Poly(A)-Binding Proteins / metabolism
  • RNA Nucleotidyltransferases / metabolism*
  • RNA Stability*
  • RNA, Messenger / metabolism
  • Uridine Monophosphate / metabolism


  • DNA-Binding Proteins
  • MicroRNAs
  • Poly(A)-Binding Proteins
  • RNA, Messenger
  • TUT4 protein, human
  • Poly A
  • Uridine Monophosphate
  • RNA Nucleotidyltransferases
  • TUT7 protein, human

Associated data

  • GEO/GSE59628