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

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.

Publication DOI: https://doi.org/10.1016/j.cell.2017.01.019
Divisions: College of Health & Life Sciences > Aston Medical School
Additional Information: © 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/).
Uncontrolled Keywords: alternative last exon splicing,ASCC3,DNA damage response,lncRNA,non-coding RNA,RNA polymerase II,transcript elongation,UV-irradiation,Biochemistry, Genetics and Molecular Biology(all)
Publication ISSN: 1097-4172
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.sci ... 0673?via%3Dihub (Publisher URL)
PURE Output Type: Article
Published Date: 2017-02-23
Accepted Date: 2017-01-18
Authors: Williamson, Laura
Saponaro, Marco
Boeing, Stefan
East, Philip
Mitter, Richard
Kantidakis, Theodoros (ORCID Profile 0000-0002-3515-5235)
Kelly, Gavin P.
Lobley, Anna
Walker, Jane
Spencer-Dene, Bradley
Howell, Michael
Stewart, Aengus
Svejstrup, Jesper Q.

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