Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1
Abstract Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of fibrillary material in the convent...
Gespeichert in:
| Veröffentlicht in: | Human molecular genetics 2020-07, Vol.29 (12), p.1986-1995 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1995 |
|---|---|
| container_issue | 12 |
| container_start_page | 1986 |
| container_title | Human molecular genetics |
| container_volume | 29 |
| creator | Schmitt, Heather M Johnson, William M Aboobakar, Inas F Strickland, Shelby Gomez-Caraballo, María Parker, Megan Finnegan, Laura Corcoran, David L Skiba, Nikolai P Allingham, R Rand Hauser, Michael A Stamer, W Daniel |
| description | Abstract
Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of fibrillary material in the conventional outflow pathway. However, the molecular mechanisms that drive pathogenesis and genetic risk remain poorly understood. PEX glaucoma-associated single-nucleotide polymorphisms are located in and affect activity of the promoter of LOXL1-AS1, a long non-coding RNA (lncRNA). Nuclear and non-nuclear lncRNAs regulate a host of biological processes, and when dysregulated, contribute to disease. Here we report that LOXL1-AS1 localizes to the nucleus where it selectively binds to the mRNA processing protein, heterogeneous nuclear ribonucleoprotein-L (hnRNPL). Both components of this complex are critical for the regulation of global gene expression in ocular cells, making LOXL1-AS1 a prime target for investigation in PEX syndrome and glaucoma. |
| doi_str_mv | 10.1093/hmg/ddaa021 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7390937</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/hmg/ddaa021</oup_id><sourcerecordid>2353017904</sourcerecordid><originalsourceid>FETCH-LOGICAL-c342t-6ef88872f96f18c4a54495014542e201cede1ebb86c3c714904871ade7fb47dc3</originalsourceid><addsrcrecordid>eNp9kUFP3DAQRq2qVVloT71XPlWVIGDH3ji5VFohoEgRIApSb5Zjj1lXiZ3GCWXv_HC83S2iF06WPG_e2PMh9ImSQ0oqdrTs7o6MUYrk9A2aUV6QLCcle4tmpCp4VlSk2EG7Mf4ihBacifdoh-WECc7pDD2eG_Cjs06r0QWPlTdY6dHdu3GFg8XjErCdvF4XVYt16PoWHnAD4x8Aj5f--uKq_tu1JvsIkwnwYEPrNr648mYIHWQqxqDTJRjcen19sTjA9eXPmmaLH_QDemdVG-Hj9txDt6cnN8ffs_ry7Px4UWea8XzMCrBlWYrcVoWlpeZqznk1J5TPeQ45oRoMUGiastBMC8orwktBlQFhGy6MZnvo28bbT00HRqefD6qV_eA6NaxkUE7-X_FuKe_CvRSsSpsWSfB1KxjC7wniKDsXNbSt8hCmKHM2Z4SKNDih-xtUDyHGAezzGErkOjeZcpPb3BL9-eXLntl_QSXgywYIU_-q6QkXCqQR</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2353017904</pqid></control><display><type>article</type><title>Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Schmitt, Heather M ; Johnson, William M ; Aboobakar, Inas F ; Strickland, Shelby ; Gomez-Caraballo, María ; Parker, Megan ; Finnegan, Laura ; Corcoran, David L ; Skiba, Nikolai P ; Allingham, R Rand ; Hauser, Michael A ; Stamer, W Daniel</creator><creatorcontrib>Schmitt, Heather M ; Johnson, William M ; Aboobakar, Inas F ; Strickland, Shelby ; Gomez-Caraballo, María ; Parker, Megan ; Finnegan, Laura ; Corcoran, David L ; Skiba, Nikolai P ; Allingham, R Rand ; Hauser, Michael A ; Stamer, W Daniel</creatorcontrib><description>Abstract
Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of fibrillary material in the conventional outflow pathway. However, the molecular mechanisms that drive pathogenesis and genetic risk remain poorly understood. PEX glaucoma-associated single-nucleotide polymorphisms are located in and affect activity of the promoter of LOXL1-AS1, a long non-coding RNA (lncRNA). Nuclear and non-nuclear lncRNAs regulate a host of biological processes, and when dysregulated, contribute to disease. Here we report that LOXL1-AS1 localizes to the nucleus where it selectively binds to the mRNA processing protein, heterogeneous nuclear ribonucleoprotein-L (hnRNPL). Both components of this complex are critical for the regulation of global gene expression in ocular cells, making LOXL1-AS1 a prime target for investigation in PEX syndrome and glaucoma.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddaa021</identifier><identifier>PMID: 32037441</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Amino Acid Oxidoreductases - genetics ; Exfoliation Syndrome - genetics ; Exfoliation Syndrome - pathology ; Gene Expression Regulation - genetics ; Genetic Predisposition to Disease ; Glaucoma, Open-Angle - genetics ; Glaucoma, Open-Angle - pathology ; Humans ; Multiprotein Complexes - genetics ; Polymorphism, Single Nucleotide - genetics ; Promoter Regions, Genetic - genetics ; Ribonucleoproteins - genetics ; RNA, Long Noncoding - genetics</subject><ispartof>Human molecular genetics, 2020-07, Vol.29 (12), p.1986-1995</ispartof><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c342t-6ef88872f96f18c4a54495014542e201cede1ebb86c3c714904871ade7fb47dc3</citedby><cites>FETCH-LOGICAL-c342t-6ef88872f96f18c4a54495014542e201cede1ebb86c3c714904871ade7fb47dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1583,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32037441$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmitt, Heather M</creatorcontrib><creatorcontrib>Johnson, William M</creatorcontrib><creatorcontrib>Aboobakar, Inas F</creatorcontrib><creatorcontrib>Strickland, Shelby</creatorcontrib><creatorcontrib>Gomez-Caraballo, María</creatorcontrib><creatorcontrib>Parker, Megan</creatorcontrib><creatorcontrib>Finnegan, Laura</creatorcontrib><creatorcontrib>Corcoran, David L</creatorcontrib><creatorcontrib>Skiba, Nikolai P</creatorcontrib><creatorcontrib>Allingham, R Rand</creatorcontrib><creatorcontrib>Hauser, Michael A</creatorcontrib><creatorcontrib>Stamer, W Daniel</creatorcontrib><title>Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><description>Abstract
Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of fibrillary material in the conventional outflow pathway. However, the molecular mechanisms that drive pathogenesis and genetic risk remain poorly understood. PEX glaucoma-associated single-nucleotide polymorphisms are located in and affect activity of the promoter of LOXL1-AS1, a long non-coding RNA (lncRNA). Nuclear and non-nuclear lncRNAs regulate a host of biological processes, and when dysregulated, contribute to disease. Here we report that LOXL1-AS1 localizes to the nucleus where it selectively binds to the mRNA processing protein, heterogeneous nuclear ribonucleoprotein-L (hnRNPL). Both components of this complex are critical for the regulation of global gene expression in ocular cells, making LOXL1-AS1 a prime target for investigation in PEX syndrome and glaucoma.</description><subject>Amino Acid Oxidoreductases - genetics</subject><subject>Exfoliation Syndrome - genetics</subject><subject>Exfoliation Syndrome - pathology</subject><subject>Gene Expression Regulation - genetics</subject><subject>Genetic Predisposition to Disease</subject><subject>Glaucoma, Open-Angle - genetics</subject><subject>Glaucoma, Open-Angle - pathology</subject><subject>Humans</subject><subject>Multiprotein Complexes - genetics</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Ribonucleoproteins - genetics</subject><subject>RNA, Long Noncoding - genetics</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFP3DAQRq2qVVloT71XPlWVIGDH3ji5VFohoEgRIApSb5Zjj1lXiZ3GCWXv_HC83S2iF06WPG_e2PMh9ImSQ0oqdrTs7o6MUYrk9A2aUV6QLCcle4tmpCp4VlSk2EG7Mf4ihBacifdoh-WECc7pDD2eG_Cjs06r0QWPlTdY6dHdu3GFg8XjErCdvF4XVYt16PoWHnAD4x8Aj5f--uKq_tu1JvsIkwnwYEPrNr648mYIHWQqxqDTJRjcen19sTjA9eXPmmaLH_QDemdVG-Hj9txDt6cnN8ffs_ry7Px4UWea8XzMCrBlWYrcVoWlpeZqznk1J5TPeQ45oRoMUGiastBMC8orwktBlQFhGy6MZnvo28bbT00HRqefD6qV_eA6NaxkUE7-X_FuKe_CvRSsSpsWSfB1KxjC7wniKDsXNbSt8hCmKHM2Z4SKNDih-xtUDyHGAezzGErkOjeZcpPb3BL9-eXLntl_QSXgywYIU_-q6QkXCqQR</recordid><startdate>20200729</startdate><enddate>20200729</enddate><creator>Schmitt, Heather M</creator><creator>Johnson, William M</creator><creator>Aboobakar, Inas F</creator><creator>Strickland, Shelby</creator><creator>Gomez-Caraballo, María</creator><creator>Parker, Megan</creator><creator>Finnegan, Laura</creator><creator>Corcoran, David L</creator><creator>Skiba, Nikolai P</creator><creator>Allingham, R Rand</creator><creator>Hauser, Michael A</creator><creator>Stamer, W Daniel</creator><general>Oxford University 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>5PM</scope></search><sort><creationdate>20200729</creationdate><title>Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1</title><author>Schmitt, Heather M ; Johnson, William M ; Aboobakar, Inas F ; Strickland, Shelby ; Gomez-Caraballo, María ; Parker, Megan ; Finnegan, Laura ; Corcoran, David L ; Skiba, Nikolai P ; Allingham, R Rand ; Hauser, Michael A ; Stamer, W Daniel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c342t-6ef88872f96f18c4a54495014542e201cede1ebb86c3c714904871ade7fb47dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Amino Acid Oxidoreductases - genetics</topic><topic>Exfoliation Syndrome - genetics</topic><topic>Exfoliation Syndrome - pathology</topic><topic>Gene Expression Regulation - genetics</topic><topic>Genetic Predisposition to Disease</topic><topic>Glaucoma, Open-Angle - genetics</topic><topic>Glaucoma, Open-Angle - pathology</topic><topic>Humans</topic><topic>Multiprotein Complexes - genetics</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Ribonucleoproteins - genetics</topic><topic>RNA, Long Noncoding - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmitt, Heather M</creatorcontrib><creatorcontrib>Johnson, William M</creatorcontrib><creatorcontrib>Aboobakar, Inas F</creatorcontrib><creatorcontrib>Strickland, Shelby</creatorcontrib><creatorcontrib>Gomez-Caraballo, María</creatorcontrib><creatorcontrib>Parker, Megan</creatorcontrib><creatorcontrib>Finnegan, Laura</creatorcontrib><creatorcontrib>Corcoran, David L</creatorcontrib><creatorcontrib>Skiba, Nikolai P</creatorcontrib><creatorcontrib>Allingham, R Rand</creatorcontrib><creatorcontrib>Hauser, Michael A</creatorcontrib><creatorcontrib>Stamer, W Daniel</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>PubMed Central (Full Participant titles)</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmitt, Heather M</au><au>Johnson, William M</au><au>Aboobakar, Inas F</au><au>Strickland, Shelby</au><au>Gomez-Caraballo, María</au><au>Parker, Megan</au><au>Finnegan, Laura</au><au>Corcoran, David L</au><au>Skiba, Nikolai P</au><au>Allingham, R Rand</au><au>Hauser, Michael A</au><au>Stamer, W Daniel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2020-07-29</date><risdate>2020</risdate><volume>29</volume><issue>12</issue><spage>1986</spage><epage>1995</epage><pages>1986-1995</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><abstract>Abstract
Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of fibrillary material in the conventional outflow pathway. However, the molecular mechanisms that drive pathogenesis and genetic risk remain poorly understood. PEX glaucoma-associated single-nucleotide polymorphisms are located in and affect activity of the promoter of LOXL1-AS1, a long non-coding RNA (lncRNA). Nuclear and non-nuclear lncRNAs regulate a host of biological processes, and when dysregulated, contribute to disease. Here we report that LOXL1-AS1 localizes to the nucleus where it selectively binds to the mRNA processing protein, heterogeneous nuclear ribonucleoprotein-L (hnRNPL). Both components of this complex are critical for the regulation of global gene expression in ocular cells, making LOXL1-AS1 a prime target for investigation in PEX syndrome and glaucoma.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>32037441</pmid><doi>10.1093/hmg/ddaa021</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0964-6906 |
| ispartof | Human molecular genetics, 2020-07, Vol.29 (12), p.1986-1995 |
| issn | 0964-6906 1460-2083 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7390937 |
| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Amino Acid Oxidoreductases - genetics Exfoliation Syndrome - genetics Exfoliation Syndrome - pathology Gene Expression Regulation - genetics Genetic Predisposition to Disease Glaucoma, Open-Angle - genetics Glaucoma, Open-Angle - pathology Humans Multiprotein Complexes - genetics Polymorphism, Single Nucleotide - genetics Promoter Regions, Genetic - genetics Ribonucleoproteins - genetics RNA, Long Noncoding - genetics |
| title | Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T10%3A20%3A44IST&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=Identification%20and%20activity%20of%20the%20functional%20complex%20between%20hnRNPL%20and%20the%20pseudoexfoliation%20syndrome-associated%20lncRNA,%20LOXL1-AS1&rft.jtitle=Human%20molecular%20genetics&rft.au=Schmitt,%20Heather%20M&rft.date=2020-07-29&rft.volume=29&rft.issue=12&rft.spage=1986&rft.epage=1995&rft.pages=1986-1995&rft.issn=0964-6906&rft.eissn=1460-2083&rft_id=info:doi/10.1093/hmg/ddaa021&rft_dat=%3Cproquest_pubme%3E2353017904%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=2353017904&rft_id=info:pmid/32037441&rft_oup_id=10.1093/hmg/ddaa021&rfr_iscdi=true |