Unusual Processing Generates SPA LncRNAs that Sequester Multiple RNA Binding Proteins
We identify a type of polycistronic transcript-derived long noncoding RNAs (lncRNAs) that are 5′ small nucleolar RNA (snoRNA) capped and 3′ polyadenylated (SPAs). SPA processing is associated with nascent mRNA 3′ processing and kinetic competition between XRN2 trimming and Pol II elongation. Followi...
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Veröffentlicht in: | Molecular cell 2016-11, Vol.64 (3), p.534-548 |
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creator | Wu, Huang Yin, Qing-Fei Luo, Zheng Yao, Run-Wen Zheng, Chuan-Chuan Zhang, Jun Xiang, Jian-Feng Yang, Li Chen, Ling-Ling |
description | We identify a type of polycistronic transcript-derived long noncoding RNAs (lncRNAs) that are 5′ small nucleolar RNA (snoRNA) capped and 3′ polyadenylated (SPAs). SPA processing is associated with nascent mRNA 3′ processing and kinetic competition between XRN2 trimming and Pol II elongation. Following cleavage/polyadenylation of its upstream gene, the downstream uncapped pre-SPA is trimmed by XRN2 until this exonuclease reaches the co-transcriptionally assembled snoRNP. This snoRNP complex prevents further degradation, generates a snoRNA 5′ end, and allows continuous Pol II elongation. The imprinted 15q11-q13 encodes two SPAs that are deleted in Prader-Willi syndrome (PWS) patients. These lncRNAs form a nuclear accumulation that is enriched in RNA binding proteins (RBPs) including TDP43, RBFOX2, and hnRNP M. Generation of a human PWS cellular model by depleting these lncRNAs results in altered patterns of RBPs binding and alternative splicing. Together, these results expand the diversity of lncRNAs and provide additional insights into PWS pathogenesis.
[Display omitted]
•Unusual processing generates 5′ SnoRNA capped and 3′ PolyAdenylated (SPA) lncRNAs•SPA processing requires a fast Pol II and snoRNP protection from XRN2 trimming•Two SPAs that sequester multiple RBPs in hESCs are absent in PWS patients•Knockout SPAs in hESCs leads to altered patterns of RBPs binding and splicing
Wu et al. report SPA lncRNAs that are capped by snoRNAs and require snoRNP complexes to protect them from trimming by XRN2. Two SPAs associated with Prader-Willi syndrome can sequester multiple RBPs and regulate alternative splicing. |
doi_str_mv | 10.1016/j.molcel.2016.10.007 |
format | Article |
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[Display omitted]
•Unusual processing generates 5′ SnoRNA capped and 3′ PolyAdenylated (SPA) lncRNAs•SPA processing requires a fast Pol II and snoRNP protection from XRN2 trimming•Two SPAs that sequester multiple RBPs in hESCs are absent in PWS patients•Knockout SPAs in hESCs leads to altered patterns of RBPs binding and splicing
Wu et al. report SPA lncRNAs that are capped by snoRNAs and require snoRNP complexes to protect them from trimming by XRN2. Two SPAs associated with Prader-Willi syndrome can sequester multiple RBPs and regulate alternative splicing.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2016.10.007</identifier><identifier>PMID: 27871485</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alternative Splicing ; Base Sequence ; Chromosomes, Human, Pair 15 ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Exoribonucleases - genetics ; Exoribonucleases - metabolism ; Genetic Loci ; Genomic Imprinting ; Heterogeneous-Nuclear Ribonucleoprotein Group M - genetics ; Heterogeneous-Nuclear Ribonucleoprotein Group M - metabolism ; Human Embryonic Stem Cells - metabolism ; Human Embryonic Stem Cells - pathology ; Humans ; Prader-Willi Syndrome - genetics ; Prader-Willi Syndrome - metabolism ; Prader-Willi Syndrome - pathology ; Protein Binding ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; RNA Polymerase II - genetics ; RNA Polymerase II - metabolism ; RNA Splicing Factors - genetics ; RNA Splicing Factors - metabolism ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; RNA, Small Nucleolar - genetics ; RNA, Small Nucleolar - metabolism ; Sequence Deletion ; Transcription, Genetic</subject><ispartof>Molecular cell, 2016-11, Vol.64 (3), p.534-548</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-8ebc56b939231833234293ec820c810a4890db20700051516b37ac77cbee120b3</citedby><cites>FETCH-LOGICAL-c408t-8ebc56b939231833234293ec820c810a4890db20700051516b37ac77cbee120b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S109727651630630X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27871485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Huang</creatorcontrib><creatorcontrib>Yin, Qing-Fei</creatorcontrib><creatorcontrib>Luo, Zheng</creatorcontrib><creatorcontrib>Yao, Run-Wen</creatorcontrib><creatorcontrib>Zheng, Chuan-Chuan</creatorcontrib><creatorcontrib>Zhang, Jun</creatorcontrib><creatorcontrib>Xiang, Jian-Feng</creatorcontrib><creatorcontrib>Yang, Li</creatorcontrib><creatorcontrib>Chen, Ling-Ling</creatorcontrib><title>Unusual Processing Generates SPA LncRNAs that Sequester Multiple RNA Binding Proteins</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>We identify a type of polycistronic transcript-derived long noncoding RNAs (lncRNAs) that are 5′ small nucleolar RNA (snoRNA) capped and 3′ polyadenylated (SPAs). SPA processing is associated with nascent mRNA 3′ processing and kinetic competition between XRN2 trimming and Pol II elongation. Following cleavage/polyadenylation of its upstream gene, the downstream uncapped pre-SPA is trimmed by XRN2 until this exonuclease reaches the co-transcriptionally assembled snoRNP. This snoRNP complex prevents further degradation, generates a snoRNA 5′ end, and allows continuous Pol II elongation. The imprinted 15q11-q13 encodes two SPAs that are deleted in Prader-Willi syndrome (PWS) patients. These lncRNAs form a nuclear accumulation that is enriched in RNA binding proteins (RBPs) including TDP43, RBFOX2, and hnRNP M. Generation of a human PWS cellular model by depleting these lncRNAs results in altered patterns of RBPs binding and alternative splicing. Together, these results expand the diversity of lncRNAs and provide additional insights into PWS pathogenesis.
[Display omitted]
•Unusual processing generates 5′ SnoRNA capped and 3′ PolyAdenylated (SPA) lncRNAs•SPA processing requires a fast Pol II and snoRNP protection from XRN2 trimming•Two SPAs that sequester multiple RBPs in hESCs are absent in PWS patients•Knockout SPAs in hESCs leads to altered patterns of RBPs binding and splicing
Wu et al. report SPA lncRNAs that are capped by snoRNAs and require snoRNP complexes to protect them from trimming by XRN2. Two SPAs associated with Prader-Willi syndrome can sequester multiple RBPs and regulate alternative splicing.</description><subject>Alternative Splicing</subject><subject>Base Sequence</subject><subject>Chromosomes, Human, Pair 15</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Exoribonucleases - genetics</subject><subject>Exoribonucleases - metabolism</subject><subject>Genetic Loci</subject><subject>Genomic Imprinting</subject><subject>Heterogeneous-Nuclear Ribonucleoprotein Group M - genetics</subject><subject>Heterogeneous-Nuclear Ribonucleoprotein Group M - metabolism</subject><subject>Human Embryonic Stem Cells - metabolism</subject><subject>Human Embryonic Stem Cells - pathology</subject><subject>Humans</subject><subject>Prader-Willi Syndrome - genetics</subject><subject>Prader-Willi Syndrome - metabolism</subject><subject>Prader-Willi Syndrome - pathology</subject><subject>Protein Binding</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>RNA Polymerase II - genetics</subject><subject>RNA Polymerase II - metabolism</subject><subject>RNA Splicing Factors - genetics</subject><subject>RNA Splicing Factors - metabolism</subject><subject>RNA, Long Noncoding - genetics</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>RNA, Small Nucleolar - genetics</subject><subject>RNA, Small Nucleolar - metabolism</subject><subject>Sequence Deletion</subject><subject>Transcription, Genetic</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EoqXwBwh5ySZl7Dixs0EqFRSkAhWlaytxpuAqTYqdIPH3uLSwZDWe8b3zOIScMxgyYOnVarhuKoPVkIcslIYA8oD0GWQyEiwVh_s3l2nSIyferwCYSFR2THpcKsmESvpksag73-UVnbnGoPe2fqMTrNHlLXo6n43otDYvTyNP2_e8pXP86NC36OhjV7V2UyENn_TG1uXWGZq0aGt_So6WeeXxbB8HZHF3-zq-j6bPk4fxaBoZAaqNFBYmSYssznjMVBzzWPAsRqM4GMUgFyqDsuAgASBhCUuLWOZGSlMgMg5FPCCXu74b1_wsptfWByZVXmPTec2U4EmWhcODVOykxjXeO1zqjbPr3H1pBnoLVK_0DqjeAt1WA9Bgu9hP6Io1ln-mX4JBcL0TYLjz06LT3lisDZbWoWl12dj_J3wDEpGG9A</recordid><startdate>20161103</startdate><enddate>20161103</enddate><creator>Wu, Huang</creator><creator>Yin, Qing-Fei</creator><creator>Luo, Zheng</creator><creator>Yao, Run-Wen</creator><creator>Zheng, Chuan-Chuan</creator><creator>Zhang, Jun</creator><creator>Xiang, Jian-Feng</creator><creator>Yang, Li</creator><creator>Chen, Ling-Ling</creator><general>Elsevier Inc</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></search><sort><creationdate>20161103</creationdate><title>Unusual Processing Generates SPA LncRNAs that Sequester Multiple RNA Binding Proteins</title><author>Wu, Huang ; Yin, Qing-Fei ; Luo, Zheng ; Yao, Run-Wen ; Zheng, Chuan-Chuan ; Zhang, Jun ; Xiang, Jian-Feng ; Yang, Li ; Chen, Ling-Ling</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-8ebc56b939231833234293ec820c810a4890db20700051516b37ac77cbee120b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alternative Splicing</topic><topic>Base Sequence</topic><topic>Chromosomes, Human, Pair 15</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Exoribonucleases - genetics</topic><topic>Exoribonucleases - metabolism</topic><topic>Genetic Loci</topic><topic>Genomic Imprinting</topic><topic>Heterogeneous-Nuclear Ribonucleoprotein Group M - genetics</topic><topic>Heterogeneous-Nuclear Ribonucleoprotein Group M - metabolism</topic><topic>Human Embryonic Stem Cells - metabolism</topic><topic>Human Embryonic Stem Cells - pathology</topic><topic>Humans</topic><topic>Prader-Willi Syndrome - genetics</topic><topic>Prader-Willi Syndrome - metabolism</topic><topic>Prader-Willi Syndrome - pathology</topic><topic>Protein Binding</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>RNA Polymerase II - genetics</topic><topic>RNA Polymerase II - metabolism</topic><topic>RNA Splicing Factors - genetics</topic><topic>RNA Splicing Factors - metabolism</topic><topic>RNA, Long Noncoding - genetics</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>RNA, Small Nucleolar - genetics</topic><topic>RNA, Small Nucleolar - metabolism</topic><topic>Sequence Deletion</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Huang</creatorcontrib><creatorcontrib>Yin, Qing-Fei</creatorcontrib><creatorcontrib>Luo, Zheng</creatorcontrib><creatorcontrib>Yao, Run-Wen</creatorcontrib><creatorcontrib>Zheng, Chuan-Chuan</creatorcontrib><creatorcontrib>Zhang, Jun</creatorcontrib><creatorcontrib>Xiang, Jian-Feng</creatorcontrib><creatorcontrib>Yang, Li</creatorcontrib><creatorcontrib>Chen, Ling-Ling</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><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Huang</au><au>Yin, Qing-Fei</au><au>Luo, Zheng</au><au>Yao, Run-Wen</au><au>Zheng, Chuan-Chuan</au><au>Zhang, Jun</au><au>Xiang, Jian-Feng</au><au>Yang, Li</au><au>Chen, Ling-Ling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unusual Processing Generates SPA LncRNAs that Sequester Multiple RNA Binding Proteins</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2016-11-03</date><risdate>2016</risdate><volume>64</volume><issue>3</issue><spage>534</spage><epage>548</epage><pages>534-548</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>We identify a type of polycistronic transcript-derived long noncoding RNAs (lncRNAs) that are 5′ small nucleolar RNA (snoRNA) capped and 3′ polyadenylated (SPAs). SPA processing is associated with nascent mRNA 3′ processing and kinetic competition between XRN2 trimming and Pol II elongation. Following cleavage/polyadenylation of its upstream gene, the downstream uncapped pre-SPA is trimmed by XRN2 until this exonuclease reaches the co-transcriptionally assembled snoRNP. This snoRNP complex prevents further degradation, generates a snoRNA 5′ end, and allows continuous Pol II elongation. The imprinted 15q11-q13 encodes two SPAs that are deleted in Prader-Willi syndrome (PWS) patients. These lncRNAs form a nuclear accumulation that is enriched in RNA binding proteins (RBPs) including TDP43, RBFOX2, and hnRNP M. Generation of a human PWS cellular model by depleting these lncRNAs results in altered patterns of RBPs binding and alternative splicing. Together, these results expand the diversity of lncRNAs and provide additional insights into PWS pathogenesis.
[Display omitted]
•Unusual processing generates 5′ SnoRNA capped and 3′ PolyAdenylated (SPA) lncRNAs•SPA processing requires a fast Pol II and snoRNP protection from XRN2 trimming•Two SPAs that sequester multiple RBPs in hESCs are absent in PWS patients•Knockout SPAs in hESCs leads to altered patterns of RBPs binding and splicing
Wu et al. report SPA lncRNAs that are capped by snoRNAs and require snoRNP complexes to protect them from trimming by XRN2. Two SPAs associated with Prader-Willi syndrome can sequester multiple RBPs and regulate alternative splicing.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27871485</pmid><doi>10.1016/j.molcel.2016.10.007</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Alternative Splicing Base Sequence Chromosomes, Human, Pair 15 DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Exoribonucleases - genetics Exoribonucleases - metabolism Genetic Loci Genomic Imprinting Heterogeneous-Nuclear Ribonucleoprotein Group M - genetics Heterogeneous-Nuclear Ribonucleoprotein Group M - metabolism Human Embryonic Stem Cells - metabolism Human Embryonic Stem Cells - pathology Humans Prader-Willi Syndrome - genetics Prader-Willi Syndrome - metabolism Prader-Willi Syndrome - pathology Protein Binding Repressor Proteins - genetics Repressor Proteins - metabolism RNA Polymerase II - genetics RNA Polymerase II - metabolism RNA Splicing Factors - genetics RNA Splicing Factors - metabolism RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism RNA, Small Nucleolar - genetics RNA, Small Nucleolar - metabolism Sequence Deletion Transcription, Genetic |
title | Unusual Processing Generates SPA LncRNAs that Sequester Multiple RNA Binding Proteins |
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