Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments

Nat Commun. 2017 Dec 11;8(1):2029. doi: 10.1038/s41467-017-02099-7.


The majority of mammalian genes contain one or more alternative polyadenylation sites. Choice of polyadenylation sites was suggested as one of the underlying mechanisms for generating longer/shorter transcript isoforms. Here, we demonstrate that mature mRNA transcripts can undergo additional cleavage and polyadenylation at a proximal internal site in the 3'-UTR, resulting in two stable, autonomous, RNA fragments: a coding sequence with a shorter 3'-UTR (body) and an uncapped 3'-UTR sequence downstream of the cleavage point (tail). Analyses of the human transcriptome has revealed thousands of such cleavage positions, suggesting a widespread post-transcriptional phenomenon producing thousands of stable 3'-UTR RNA tails that exist alongside their transcripts of origin. By analyzing the impact of microRNAs, we observed a significantly stronger effect for microRNA regulation at the body compared to the tail fragments. Our findings open a variety of future research prospects and call for a new perspective on 3'-UTR-dependent gene regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Animals
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • Open Reading Frames / genetics
  • Polyadenylation
  • RNA Caps
  • RNA Isoforms / genetics*
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / genetics*


  • 3' Untranslated Regions
  • MicroRNAs
  • RNA Caps
  • RNA Isoforms
  • RNA, Messenger