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

Authors :
Richard Mitter
Gavin Kelly
Jesper Q. Svejstrup
Anna Lobley
Marco Saponaro
Michael Howell
Laura Williamson
Theodoros Kantidakis
Bradley Spencer-Dene
Philip East
Stefan Boeing
Jane Walker
Aengus Stewart
Source :
Cell
Publication Year :
2017

Abstract

Summary 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.<br />Graphical Abstract<br />Highlights • UV elicits elongation slowdown and restricts transcription to the 5′ end of genes • UV induces a switch from long to short alternative last exon (ALE) transcript isoforms • ASCC3 short and long ALE isoforms have antagonistic functions in the UV response • The UV-induced ASCC3 short isoform functions as a long non-coding RNA<br />UV damage generates a functional non-coding RNA through alternative pre-mRNA processing of a damage response factor transcript, identifying a pathway for repurposing protein coding genes under selective conditions.

Details

Language :
English
ISSN :
10974172
Database :
OpenAIRE
Journal :
Cell
Accession number :
edsair.doi.dedup.....02a756e4c3ce1ef7dac74ac07c56c6cf