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

doi:10.1016/j.cell.2017.01.019

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

Cell. 2017 Feb 23;168(5):843-855.e13. doi: 10.1016/j.cell.2017.01.019. Epub 2017 Feb 16.

Authors

Affiliations

¹ Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
² 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.
³ 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.
⁴ Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
⁵ Experimental Histopathology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
⁶ High Throughput Screening Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
⁷ Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK. Electronic address: [email protected].

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.

Keywords: ASCC3; DNA damage response; RNA polymerase II; UV-irradiation; alternative last exon splicing; lncRNA; non-coding RNA; transcript elongation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing / radiation effects*
Cell Line
DNA Helicases / genetics*
Exons
Humans
RNA Polymerase II / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Untranslated / genetics*
Transcription Elongation, Genetic / radiation effects
Transcription Initiation, Genetic / radiation effects
Transcription, Genetic*
Ultraviolet Rays*

Substances

RNA, Messenger
RNA, Untranslated
RNA Polymerase II
ASCC3 protein, human
DNA Helicases

Abstract

Publication types

MeSH terms

Substances

Grants and funding