TAIL-seq: genome-wide determination of poly(A) tail length and 3' end modifications

Mol Cell. 2014 Mar 20;53(6):1044-52. doi: 10.1016/j.molcel.2014.02.007. Epub 2014 Feb 27.


Global investigation of the 3' extremity of mRNA (3'-terminome), despite its importance in gene regulation, has not been feasible due to technical challenges associated with homopolymeric sequences and relative paucity of mRNA. We here develop a method, TAIL-seq, to sequence the very end of mRNA molecules. TAIL-seq allows us to measure poly(A) tail length at the genomic scale. Median poly(A) length is 50-100 nt in HeLa and NIH 3T3 cells. Poly(A) length correlates with mRNA half-life, but not with translational efficiency. Surprisingly, we discover widespread uridylation and guanylation at the downstream of poly(A) tail. The U tails are generally attached to short poly(A) tails (<25 nt), while the G tails are found mainly on longer poly(A) tails (>40 nt), implicating their generic roles in mRNA stability control. TAIL-seq is a potent tool to dissect dynamic control of mRNA turnover and translational control, and to discover unforeseen features of RNA cleavage and tailing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Animals
  • Base Sequence
  • Gene Expression Regulation
  • Genome*
  • Guanine / metabolism
  • Half-Life
  • HeLa Cells
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Polyadenylation
  • RNA Stability*
  • Sequence Analysis, RNA / methods*
  • Signal Transduction
  • Uridine / metabolism


  • 3' Untranslated Regions
  • MicroRNAs
  • Guanine
  • Uridine

Associated data

  • GEO/GSE51299
  • GEO/GSE54114