UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene
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 ex...
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Veröffentlicht in: | Cell 2017-02, Vol.168 (5), p.843-855.e13 |
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container_title | Cell |
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creator | Williamson, Laura Saponaro, Marco Boeing, Stefan East, Philip Mitter, Richard Kantidakis, Theodoros Kelly, Gavin P. Lobley, Anna Walker, Jane Spencer-Dene, Bradley Howell, Michael Stewart, Aengus Svejstrup, Jesper Q. |
description | 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.
[Display omitted]
•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
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. |
doi_str_mv | 10.1016/j.cell.2017.01.019 |
format | Article |
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[Display omitted]
•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
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.</description><identifier>ISSN: 0092-8674</identifier><identifier>ISSN: 1097-4172</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/j.cell.2017.01.019</identifier><identifier>PMID: 28215706</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>alternative last exon splicing ; Alternative Splicing - radiation effects ; ASCC3 ; Cell Line ; DNA damage response ; DNA Helicases - genetics ; Exons ; Humans ; lncRNA ; non-coding RNA ; RNA polymerase II ; RNA Polymerase II - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA, Untranslated - genetics ; transcript elongation ; Transcription Elongation, Genetic - radiation effects ; Transcription Initiation, Genetic - radiation effects ; Transcription, Genetic ; Ultraviolet Rays ; UV-irradiation</subject><ispartof>Cell, 2017-02, Vol.168 (5), p.843-855.e13</ispartof><rights>2017 The Authors</rights><rights>Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2017 The Authors 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-2a96095cd493e8abe1cf9ea60f249b7ed37efd98abd409fcb6c5319e0ecd10cb3</citedby><cites>FETCH-LOGICAL-c455t-2a96095cd493e8abe1cf9ea60f249b7ed37efd98abd409fcb6c5319e0ecd10cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cell.2017.01.019$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28215706$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Williamson, Laura</creatorcontrib><creatorcontrib>Saponaro, Marco</creatorcontrib><creatorcontrib>Boeing, Stefan</creatorcontrib><creatorcontrib>East, Philip</creatorcontrib><creatorcontrib>Mitter, Richard</creatorcontrib><creatorcontrib>Kantidakis, Theodoros</creatorcontrib><creatorcontrib>Kelly, Gavin P.</creatorcontrib><creatorcontrib>Lobley, Anna</creatorcontrib><creatorcontrib>Walker, Jane</creatorcontrib><creatorcontrib>Spencer-Dene, Bradley</creatorcontrib><creatorcontrib>Howell, Michael</creatorcontrib><creatorcontrib>Stewart, Aengus</creatorcontrib><creatorcontrib>Svejstrup, Jesper Q.</creatorcontrib><title>UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene</title><title>Cell</title><addtitle>Cell</addtitle><description>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.
[Display omitted]
•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
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.</description><subject>alternative last exon splicing</subject><subject>Alternative Splicing - radiation effects</subject><subject>ASCC3</subject><subject>Cell Line</subject><subject>DNA damage response</subject><subject>DNA Helicases - genetics</subject><subject>Exons</subject><subject>Humans</subject><subject>lncRNA</subject><subject>non-coding RNA</subject><subject>RNA polymerase II</subject><subject>RNA Polymerase II - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Untranslated - genetics</subject><subject>transcript elongation</subject><subject>Transcription Elongation, Genetic - radiation effects</subject><subject>Transcription Initiation, Genetic - radiation effects</subject><subject>Transcription, Genetic</subject><subject>Ultraviolet Rays</subject><subject>UV-irradiation</subject><issn>0092-8674</issn><issn>1097-4172</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kVFrFDEUhYMo7Vr7B3yQPPoy601mMjMBEUpp60JpRdu-hkxyp5tlNlmTmcL-ezNuLfoiXAjkfucknEPIewZLBqz-tFkaHIYlB9YsgeWRr8iCgWyKijX8NVkASF60dVMdk7cpbQCgFUIckWPeciYaqBekv3-gqxi1dXp0wdOVt5PBRDW9Cb4wwTr_SL_fnNFxrUd6OXkzY3oY9vR2twspo-Ma6bcYRnSeXvgsQUu7_e_rH3qL9Ao9viNvej0kPH0-T8j95cXd-dfi-vZqdX52XZhKiLHgWtYghbGVLLHVHTLTS9Q19LySXYO2bLC3Mm9sBbI3XW1EySQCGsvAdOUJ-XLw3U3dFq1BP0Y9qF10Wx33Kmin_t14t1aP4UmJsuRCtNng47NBDD8nTKPaujTHrD2GKSnW5tgqwVqZUX5ATQwpRexfnmGg5oLURs1KNRekgOWZRR_-_uCL5E8jGfh8ADDH9OQwqmQceoPWRTSjssH9z_8X4ASjxA</recordid><startdate>20170223</startdate><enddate>20170223</enddate><creator>Williamson, Laura</creator><creator>Saponaro, Marco</creator><creator>Boeing, Stefan</creator><creator>East, Philip</creator><creator>Mitter, Richard</creator><creator>Kantidakis, Theodoros</creator><creator>Kelly, Gavin P.</creator><creator>Lobley, Anna</creator><creator>Walker, Jane</creator><creator>Spencer-Dene, Bradley</creator><creator>Howell, Michael</creator><creator>Stewart, Aengus</creator><creator>Svejstrup, Jesper Q.</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170223</creationdate><title>UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene</title><author>Williamson, Laura ; Saponaro, Marco ; Boeing, Stefan ; East, Philip ; Mitter, Richard ; Kantidakis, Theodoros ; Kelly, Gavin P. ; Lobley, Anna ; Walker, Jane ; Spencer-Dene, Bradley ; Howell, Michael ; Stewart, Aengus ; Svejstrup, Jesper Q.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-2a96095cd493e8abe1cf9ea60f249b7ed37efd98abd409fcb6c5319e0ecd10cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>alternative last exon splicing</topic><topic>Alternative Splicing - radiation effects</topic><topic>ASCC3</topic><topic>Cell Line</topic><topic>DNA damage response</topic><topic>DNA Helicases - genetics</topic><topic>Exons</topic><topic>Humans</topic><topic>lncRNA</topic><topic>non-coding RNA</topic><topic>RNA polymerase II</topic><topic>RNA Polymerase II - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Untranslated - genetics</topic><topic>transcript elongation</topic><topic>Transcription Elongation, Genetic - radiation effects</topic><topic>Transcription Initiation, Genetic - radiation effects</topic><topic>Transcription, Genetic</topic><topic>Ultraviolet Rays</topic><topic>UV-irradiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Williamson, Laura</creatorcontrib><creatorcontrib>Saponaro, Marco</creatorcontrib><creatorcontrib>Boeing, Stefan</creatorcontrib><creatorcontrib>East, Philip</creatorcontrib><creatorcontrib>Mitter, Richard</creatorcontrib><creatorcontrib>Kantidakis, Theodoros</creatorcontrib><creatorcontrib>Kelly, Gavin P.</creatorcontrib><creatorcontrib>Lobley, Anna</creatorcontrib><creatorcontrib>Walker, Jane</creatorcontrib><creatorcontrib>Spencer-Dene, Bradley</creatorcontrib><creatorcontrib>Howell, Michael</creatorcontrib><creatorcontrib>Stewart, Aengus</creatorcontrib><creatorcontrib>Svejstrup, Jesper Q.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Williamson, Laura</au><au>Saponaro, Marco</au><au>Boeing, Stefan</au><au>East, Philip</au><au>Mitter, Richard</au><au>Kantidakis, Theodoros</au><au>Kelly, Gavin P.</au><au>Lobley, Anna</au><au>Walker, Jane</au><au>Spencer-Dene, Bradley</au><au>Howell, Michael</au><au>Stewart, Aengus</au><au>Svejstrup, Jesper Q.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2017-02-23</date><risdate>2017</risdate><volume>168</volume><issue>5</issue><spage>843</spage><epage>855.e13</epage><pages>843-855.e13</pages><issn>0092-8674</issn><issn>1097-4172</issn><eissn>1097-4172</eissn><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.
[Display omitted]
•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
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28215706</pmid><doi>10.1016/j.cell.2017.01.019</doi><oa>free_for_read</oa></addata></record> |
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subjects | alternative last exon splicing Alternative Splicing - radiation effects ASCC3 Cell Line DNA damage response DNA Helicases - genetics Exons Humans lncRNA non-coding RNA RNA polymerase II RNA Polymerase II - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Untranslated - genetics transcript elongation Transcription Elongation, Genetic - radiation effects Transcription Initiation, Genetic - radiation effects Transcription, Genetic Ultraviolet Rays UV-irradiation |
title | UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene |
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