TY - JOUR
T1 - UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene
AU - Williamson, Laura
AU - Saponaro, Marco
AU - Boeing, Stefan
AU - East, Philip
AU - Mitter, Richard
AU - Kantidakis, Theodoros
AU - Kelly, Gavin P.
AU - Lobley, Anna
AU - Walker, Jane
AU - Spencer-Dene, Bradley
AU - Howell, Michael
AU - Stewart, Aengus
AU - Svejstrup, Jesper Q.
N1 - © 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/).
PY - 2017/2/23
Y1 - 2017/2/23
N2 - 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.
AB - 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.
KW - alternative last exon splicing
KW - ASCC3
KW - DNA damage response
KW - lncRNA
KW - non-coding RNA
KW - RNA polymerase II
KW - transcript elongation
KW - UV-irradiation
UR - http://www.scopus.com/inward/record.url?scp=85012919200&partnerID=8YFLogxK
UR - https://www.sciencedirect.com/science/article/pii/S0092867417300673?via%3Dihub
U2 - 10.1016/j.cell.2017.01.019
DO - 10.1016/j.cell.2017.01.019
M3 - Article
C2 - 28215706
AN - SCOPUS:85012919200
SN - 0092-8674
VL - 168
SP - 843-855.e13
JO - Cell
JF - Cell
IS - 5
ER -