Widespread occurrence of non-canonical transcription termination by human RNA polymerase III

Nucleic Acids Res. 2011 Jul;39(13):5499-512. doi: 10.1093/nar/gkr074. Epub 2011 Mar 17.


Human RNA polymerase (Pol) III-transcribed genes are thought to share a simple termination signal constituted by four or more consecutive thymidine residues in the coding DNA strand, just downstream of the RNA 3'-end sequence. We found that a large set of human tRNA genes (tDNAs) do not display any T(≥4) stretch within 50 bp of 3'-flanking region. In vitro analysis of tDNAs with a distanced T(≥4) revealed the existence of non-canonical terminators resembling degenerate T(≥5) elements, which ensure significant termination but at the same time allow for the production of Pol III read-through pre-tRNAs with unusually long 3' trailers. A panel of such non-canonical signals was found to direct transcription termination of unusual Pol III-synthesized viral pre-miRNA transcripts in gammaherpesvirus 68-infected cells. Genome-wide location analysis revealed that human Pol III tends to trespass into the 3'-flanking regions of tDNAs, as expected from extensive terminator read-through. The widespread occurrence of partial termination suggests that the Pol III primary transcriptome in mammals is unexpectedly enriched in 3'-trailer sequences with the potential to contribute novel functional ncRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Flanking Region
  • Animals
  • Cell Line
  • HeLa Cells
  • Humans
  • Mice
  • RNA Polymerase III / metabolism*
  • RNA, Transfer / genetics
  • Sequence Analysis, DNA
  • Terminator Regions, Genetic*
  • Transcription, Genetic*


  • RNA, Transfer
  • RNA Polymerase III