Williamson, Laura, Saponaro, Marco, Boeing, Stefan, East, Philip, Mitter, Richard, Kantidakis, Theodoros, Kelly, Gavin P., Lobley, Anna, Walker, Jane, Spencer-Dene, Bradley, Howell, Michael, Stewart, Aengus and Svejstrup, Jesper Q. (2017). UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene. Cell, 168 (5), 843-855.e13.
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 |
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| Divisions: | College of Health & Life Sciences > Aston Medical School |
| Funding Information: | This work was supported by the Francis Crick Institute (that receives its core funding from Cancer Research UK [FC001166], the UK Medical Research Council [FC001166], and the Wellcome Trust [FC001166]) and by grants from the European Research Council, Agreements 693327 (TRANSDAM) and 268797 (TRANSINTEG). We thank The Francis Crick Advanced Sequencing Facility, the Cell Services Facility, the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant 090532/Z/09/Z) for expression array analysis, and Yang Shi for the kind gift of ASCC3 antibody. Peter Verrijzer and members of the Svejstrup laboratory are thanked for comments on the manuscript. |
| 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,General Biochemistry,Genetics and Molecular Biology |
| Publication ISSN: | 1097-4172 |
| Last Modified: | 04 Feb 2026 08:42 |
| Date Deposited: | 15 Oct 2018 14:39 |
| 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 ( 
0000-0002-3515-5235)
Kelly, Gavin P. Lobley, Anna Walker, Jane Spencer-Dene, Bradley Howell, Michael Stewart, Aengus Svejstrup, Jesper Q. |