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

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

Cancer and Genomic Sciences

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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 language	English
Pages (from-to)	843-855.e13
Journal	Cell
Volume	168
Issue number	5
Early online date	16 Feb 2017
DOIs	https://doi.org/10.1016/j.cell.2017.01.019
Publication status	Published - 23 Feb 2017

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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 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.",

author = "Laura Williamson and Marco Saponaro and Stefan Boeing and Philip East and Richard Mitter and Theodoros Kantidakis and Kelly, {Gavin P} and Anna Lobley and Jane Walker and Bradley Spencer-Dene and Michael Howell and Aengus Stewart and Svejstrup, {Jesper Q}",

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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

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 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.

AB - 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.

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DO - 10.1016/j.cell.2017.01.019

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JO - Cell

JF - Cell

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UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene

Abstract

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