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

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)
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Abstract

The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slow- down 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 iso- form, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and non-coding transcript isoforms with opposite effects on transcrip- tion recovery after UV-induced DNA damage.
Original languageEnglish
Pages (from-to)843-855.e13
JournalCell
Volume168
Issue number5
Early online date16 Feb 2017
DOIs
Publication statusPublished - 23 Feb 2017

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