UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene

Research output: Contribution to journalArticlepeer-review

Authors

  • Laura Williamson
  • Stefan Boeing
  • Philip East
  • Richard Mitter
  • Theodoros Kantidakis
  • Gavin P Kelly
  • Anna Lobley
  • Jane Walker
  • Bradley Spencer-Dene
  • Michael Howell
  • Aengus Stewart
  • Jesper Q Svejstrup

Colleges, School and Institutes

Abstract

The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slow- down of transcript elongation and restriction of gene activity to the promoter-proximal $25 kb is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter ALE isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The non-coding ASCC3 isoform counteracts the function of the protein-coding iso- form, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and non-coding transcript isoforms with opposite effects on transcrip- tion recovery after UV-induced DNA damage.

Details

Original languageEnglish
Pages (from-to)843-855.e13
JournalCell
Volume168
Issue number5
Early online date16 Feb 2017
Publication statusPublished - 23 Feb 2017