The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends
Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3' end processing signal...
Gespeichert in:
Veröffentlicht in: | Genes & development 2015-07, Vol.29 (14), p.1552-1564 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1564 |
---|---|
container_issue | 14 |
container_start_page | 1552 |
container_title | Genes & development |
container_volume | 29 |
creator | Xie, Mingyi Zhang, Wei Shu, Mei-Di Xu, Acer Lenis, Diana A DiMaio, Daniel Steitz, Joan A |
description | Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3' end processing signal (3' box), generates the 5' ends of HVS pre-miRNA hairpins. Here, we identify a novel 3' box-like sequence (miRNA 3' box) downstream from HVS pre-miRNAs that is essential for miRNA biogenesis. In vivo knockdown and rescue experiments confirmed that the 3' end processing of HVS pre-miRNAs also depends on Integrator activity. Interaction between Integrator and HVS primary miRNA (pri-miRNA) substrates that contain only the miRNA 3' box was confirmed by coimmunoprecipitation and an in situ proximity ligation assay (PLA) that we developed to localize specific transient RNA-protein interactions inside cells. Surprisingly, in contrast to snRNA 3' end processing, HVS pre-miRNA 3' end processing by Integrator can be uncoupled from transcription, enabling new approaches to study Integrator enzymology. |
doi_str_mv | 10.1101/gad.266973.115 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4526738</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1700335339</sourcerecordid><originalsourceid>FETCH-LOGICAL-c423t-516b448a2d0db7ce221f36f6b33605065430807326756f54c677a1c4ad4b09963</originalsourceid><addsrcrecordid>eNqNkc9LHTEQx0Op1Ffba4-SW3vZ5-T37kUQsVaQCmLPIZvNvk3Z3axJVup_38izUm9CSJjkM9-ZyRehLwS2hAA52ZluS6VsFCuxeIc2RPCmElyp92gDdQNVw2RziD6m9BsAJEj5AR1SSSk0jdqg4W5weAgp46s5u100OURsw7SM7g82NifsZ5yjmZONfsk-zJWfO7e4ss0ZTyavJadc49DjwcXFpQcf14Qnb2O4_XmG2Vdc4PQJHfRmTO7z83mEfn2_uDv_UV3fXF6dn11XllOWK0Fky3ltaAddq6yjlPRM9rJlTIIAKTiDGhSjUgnZC26lUoZYbjrelokkO0Kne91lbSfX2dJlNKNeop9MfNTBeP36ZfaD3oUHzUXRZHUR-PYsEMP96lLWk0_WjaOZXViTJqV4TXlZb0ABGBOMNQXd7tHyKylF1790REA_OamLk3rvZIlFSTj-f44X_J917C9ropqD</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1700335339</pqid></control><display><type>article</type><title>The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Xie, Mingyi ; Zhang, Wei ; Shu, Mei-Di ; Xu, Acer ; Lenis, Diana A ; DiMaio, Daniel ; Steitz, Joan A</creator><creatorcontrib>Xie, Mingyi ; Zhang, Wei ; Shu, Mei-Di ; Xu, Acer ; Lenis, Diana A ; DiMaio, Daniel ; Steitz, Joan A</creatorcontrib><description>Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3' end processing signal (3' box), generates the 5' ends of HVS pre-miRNA hairpins. Here, we identify a novel 3' box-like sequence (miRNA 3' box) downstream from HVS pre-miRNAs that is essential for miRNA biogenesis. In vivo knockdown and rescue experiments confirmed that the 3' end processing of HVS pre-miRNAs also depends on Integrator activity. Interaction between Integrator and HVS primary miRNA (pri-miRNA) substrates that contain only the miRNA 3' box was confirmed by coimmunoprecipitation and an in situ proximity ligation assay (PLA) that we developed to localize specific transient RNA-protein interactions inside cells. Surprisingly, in contrast to snRNA 3' end processing, HVS pre-miRNA 3' end processing by Integrator can be uncoupled from transcription, enabling new approaches to study Integrator enzymology.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.266973.115</identifier><identifier>PMID: 26220997</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Gene Knockdown Techniques ; HEK293 Cells ; HeLa Cells ; Herpesvirus 2, Saimiriine - genetics ; Herpesvirus 2, Saimiriine - metabolism ; Herpesvirus saimiri ; Host-Pathogen Interactions - genetics ; Humans ; Immunoprecipitation ; MicroRNAs - chemistry ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Multiprotein Complexes - genetics ; Multiprotein Complexes - metabolism ; Research Paper ; RNA 3' End Processing - genetics ; RNA 3' End Processing - physiology ; RNA Precursors - genetics ; RNA Precursors - metabolism ; RNA, Small Nuclear - metabolism ; Transcription, Genetic</subject><ispartof>Genes & development, 2015-07, Vol.29 (14), p.1552-1564</ispartof><rights>2015 Xie et al.; Published by Cold Spring Harbor Laboratory Press.</rights><rights>2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-516b448a2d0db7ce221f36f6b33605065430807326756f54c677a1c4ad4b09963</citedby><cites>FETCH-LOGICAL-c423t-516b448a2d0db7ce221f36f6b33605065430807326756f54c677a1c4ad4b09963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526738/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526738/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26220997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xie, Mingyi</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Shu, Mei-Di</creatorcontrib><creatorcontrib>Xu, Acer</creatorcontrib><creatorcontrib>Lenis, Diana A</creatorcontrib><creatorcontrib>DiMaio, Daniel</creatorcontrib><creatorcontrib>Steitz, Joan A</creatorcontrib><title>The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3' end processing signal (3' box), generates the 5' ends of HVS pre-miRNA hairpins. Here, we identify a novel 3' box-like sequence (miRNA 3' box) downstream from HVS pre-miRNAs that is essential for miRNA biogenesis. In vivo knockdown and rescue experiments confirmed that the 3' end processing of HVS pre-miRNAs also depends on Integrator activity. Interaction between Integrator and HVS primary miRNA (pri-miRNA) substrates that contain only the miRNA 3' box was confirmed by coimmunoprecipitation and an in situ proximity ligation assay (PLA) that we developed to localize specific transient RNA-protein interactions inside cells. Surprisingly, in contrast to snRNA 3' end processing, HVS pre-miRNA 3' end processing by Integrator can be uncoupled from transcription, enabling new approaches to study Integrator enzymology.</description><subject>Gene Knockdown Techniques</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Herpesvirus 2, Saimiriine - genetics</subject><subject>Herpesvirus 2, Saimiriine - metabolism</subject><subject>Herpesvirus saimiri</subject><subject>Host-Pathogen Interactions - genetics</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>MicroRNAs - chemistry</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Multiprotein Complexes - genetics</subject><subject>Multiprotein Complexes - metabolism</subject><subject>Research Paper</subject><subject>RNA 3' End Processing - genetics</subject><subject>RNA 3' End Processing - physiology</subject><subject>RNA Precursors - genetics</subject><subject>RNA Precursors - metabolism</subject><subject>RNA, Small Nuclear - metabolism</subject><subject>Transcription, Genetic</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9LHTEQx0Op1Ffba4-SW3vZ5-T37kUQsVaQCmLPIZvNvk3Z3axJVup_38izUm9CSJjkM9-ZyRehLwS2hAA52ZluS6VsFCuxeIc2RPCmElyp92gDdQNVw2RziD6m9BsAJEj5AR1SSSk0jdqg4W5weAgp46s5u100OURsw7SM7g82NifsZ5yjmZONfsk-zJWfO7e4ss0ZTyavJadc49DjwcXFpQcf14Qnb2O4_XmG2Vdc4PQJHfRmTO7z83mEfn2_uDv_UV3fXF6dn11XllOWK0Fky3ltaAddq6yjlPRM9rJlTIIAKTiDGhSjUgnZC26lUoZYbjrelokkO0Kne91lbSfX2dJlNKNeop9MfNTBeP36ZfaD3oUHzUXRZHUR-PYsEMP96lLWk0_WjaOZXViTJqV4TXlZb0ABGBOMNQXd7tHyKylF1790REA_OamLk3rvZIlFSTj-f44X_J917C9ropqD</recordid><startdate>20150715</startdate><enddate>20150715</enddate><creator>Xie, Mingyi</creator><creator>Zhang, Wei</creator><creator>Shu, Mei-Di</creator><creator>Xu, Acer</creator><creator>Lenis, Diana A</creator><creator>DiMaio, Daniel</creator><creator>Steitz, Joan A</creator><general>Cold Spring Harbor Laboratory Press</general><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>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20150715</creationdate><title>The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends</title><author>Xie, Mingyi ; Zhang, Wei ; Shu, Mei-Di ; Xu, Acer ; Lenis, Diana A ; DiMaio, Daniel ; Steitz, Joan A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-516b448a2d0db7ce221f36f6b33605065430807326756f54c677a1c4ad4b09963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Gene Knockdown Techniques</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Herpesvirus 2, Saimiriine - genetics</topic><topic>Herpesvirus 2, Saimiriine - metabolism</topic><topic>Herpesvirus saimiri</topic><topic>Host-Pathogen Interactions - genetics</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>MicroRNAs - chemistry</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Multiprotein Complexes - genetics</topic><topic>Multiprotein Complexes - metabolism</topic><topic>Research Paper</topic><topic>RNA 3' End Processing - genetics</topic><topic>RNA 3' End Processing - physiology</topic><topic>RNA Precursors - genetics</topic><topic>RNA Precursors - metabolism</topic><topic>RNA, Small Nuclear - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xie, Mingyi</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Shu, Mei-Di</creatorcontrib><creatorcontrib>Xu, Acer</creatorcontrib><creatorcontrib>Lenis, Diana A</creatorcontrib><creatorcontrib>DiMaio, Daniel</creatorcontrib><creatorcontrib>Steitz, Joan A</creatorcontrib><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>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xie, Mingyi</au><au>Zhang, Wei</au><au>Shu, Mei-Di</au><au>Xu, Acer</au><au>Lenis, Diana A</au><au>DiMaio, Daniel</au><au>Steitz, Joan A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2015-07-15</date><risdate>2015</risdate><volume>29</volume><issue>14</issue><spage>1552</spage><epage>1564</epage><pages>1552-1564</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><abstract>Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3' end processing signal (3' box), generates the 5' ends of HVS pre-miRNA hairpins. Here, we identify a novel 3' box-like sequence (miRNA 3' box) downstream from HVS pre-miRNAs that is essential for miRNA biogenesis. In vivo knockdown and rescue experiments confirmed that the 3' end processing of HVS pre-miRNAs also depends on Integrator activity. Interaction between Integrator and HVS primary miRNA (pri-miRNA) substrates that contain only the miRNA 3' box was confirmed by coimmunoprecipitation and an in situ proximity ligation assay (PLA) that we developed to localize specific transient RNA-protein interactions inside cells. Surprisingly, in contrast to snRNA 3' end processing, HVS pre-miRNA 3' end processing by Integrator can be uncoupled from transcription, enabling new approaches to study Integrator enzymology.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>26220997</pmid><doi>10.1101/gad.266973.115</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0890-9369 |
ispartof | Genes & development, 2015-07, Vol.29 (14), p.1552-1564 |
issn | 0890-9369 1549-5477 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4526738 |
source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
subjects | Gene Knockdown Techniques HEK293 Cells HeLa Cells Herpesvirus 2, Saimiriine - genetics Herpesvirus 2, Saimiriine - metabolism Herpesvirus saimiri Host-Pathogen Interactions - genetics Humans Immunoprecipitation MicroRNAs - chemistry MicroRNAs - genetics MicroRNAs - metabolism Multiprotein Complexes - genetics Multiprotein Complexes - metabolism Research Paper RNA 3' End Processing - genetics RNA 3' End Processing - physiology RNA Precursors - genetics RNA Precursors - metabolism RNA, Small Nuclear - metabolism Transcription, Genetic |
title | The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T03%3A59%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20host%20Integrator%20complex%20acts%20in%20transcription-independent%20maturation%20of%20herpesvirus%20microRNA%203'%20ends&rft.jtitle=Genes%20&%20development&rft.au=Xie,%20Mingyi&rft.date=2015-07-15&rft.volume=29&rft.issue=14&rft.spage=1552&rft.epage=1564&rft.pages=1552-1564&rft.issn=0890-9369&rft.eissn=1549-5477&rft_id=info:doi/10.1101/gad.266973.115&rft_dat=%3Cproquest_pubme%3E1700335339%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1700335339&rft_id=info:pmid/26220997&rfr_iscdi=true |