UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene

Laura Williamson, Marco Saponaro, 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown 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 isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and non-coding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage.

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

Bibliographical note

© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Keywords

  • alternative last exon splicing
  • ASCC3
  • DNA damage response
  • lncRNA
  • non-coding RNA
  • RNA polymerase II
  • transcript elongation
  • UV-irradiation

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