title: 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.
authors.affiliation: Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Williamson
authors.affiliation: Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Saponaro
authors.affiliation: Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK; Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Boeing
authors.affiliation: Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: East
authors.affiliation: Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Mitter
authors.affiliation: Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kantidakis
authors.affiliation: Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Kelly
authors.affiliation: Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Lobley
authors.affiliation: Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Walker
authors.affiliation: Experimental Histopathology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Bradley
authors.initials: B
authors.lastname: Spencer-Dene
authors.affiliation: High Throughput Screening Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.affiliation: Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Aengus
authors.initials: A
authors.lastname: Stewart
authors.affiliation: Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK. Electronic address: jesper.svejstrup@crick.ac.uk.
authors.forename: Jesper Q
authors.initials: JQ
authors.lastname: Svejstrup
mesh_terms: D017398:Alternative Splicing / Q000528:radiation effects*; D002460:Cell Line; D004265:DNA Helicases / Q000235:genetics*; D005091:Exons; D006801:Humans; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics*; D061805:Transcription Elongation, Genetic / Q000528:radiation effects; D061785:Transcription Initiation, Genetic / Q000528:radiation effects; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D012333:RNA, Messenger; D022661:RNA, Untranslated; D012319:RNA Polymerase II; C584453:ASCC3 protein, human; D004265:DNA Helicases
keywords: ASCC3; DNA damage response; RNA polymerase II; UV-irradiation; alternative last exon splicing; lncRNA; non-coding RNA; transcript elongation