Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis
The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed protein that plays a critical role in polyadenylation. Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by...
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| Veröffentlicht in: | Human molecular genetics 2010-03, Vol.19 (6), p.1058-1065 |
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| creator | Apponi, Luciano H. Leung, Sara W. Williams, Kathryn R. Valentini, Sandro R. Corbett, Anita H. Pavlath, Grace K. |
| description | The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed protein that plays a critical role in polyadenylation. Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by eyelid drooping, difficulty in swallowing and weakness in the proximal limb muscles. Although significant data from in vitro biochemical assays define the function of PABPN1 in control of poly(A) tail length, little is known about the role of PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells and specifically in cells affected in OPMD, we examined the effects of PABPN1 depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and limb muscles. PABPN1 knockdown significantly decreased cell proliferation and myoblast differentiation during myogenesis in vitro. At the molecular level, PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails, demonstrating the cellular function of PABPN1 in polyadenylation control in a mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from the nucleus. Together, these experiments demonstrate that PABPN1 plays an essential role in myoblast proliferation and differentiation, suggesting that it is required for muscle regeneration and maintenance in vivo. |
| doi_str_mv | 10.1093/hmg/ddp569 |
| format | Article |
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Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by eyelid drooping, difficulty in swallowing and weakness in the proximal limb muscles. Although significant data from in vitro biochemical assays define the function of PABPN1 in control of poly(A) tail length, little is known about the role of PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells and specifically in cells affected in OPMD, we examined the effects of PABPN1 depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and limb muscles. PABPN1 knockdown significantly decreased cell proliferation and myoblast differentiation during myogenesis in vitro. At the molecular level, PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails, demonstrating the cellular function of PABPN1 in polyadenylation control in a mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from the nucleus. Together, these experiments demonstrate that PABPN1 plays an essential role in myoblast proliferation and differentiation, suggesting that it is required for muscle regeneration and maintenance in vivo.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddp569</identifier><identifier>PMID: 20035013</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Biological and medical sciences ; Cell Differentiation ; Cell Nucleus - metabolism ; Cell Proliferation ; Data processing ; Differentiation ; Eyelid ; Fundamental and applied biological sciences. Psychology ; Genetics of eukaryotes. Biological and molecular evolution ; Limbs ; Mammalian cells ; Mice ; Mice, Inbred BALB C ; Molecular and cellular biology ; mRNA ; Muscle Development ; Muscular dystrophy ; Myoblasts ; Myoblasts - cytology ; Myoblasts - metabolism ; myogenesis ; N-Terminus ; Nuclei ; Pharynx ; Poly A - metabolism ; poly(A)-binding protein ; Poly(A)-Binding Protein I - metabolism ; Poly(A)-Binding Protein II - metabolism ; Polyadenylation ; polyalanine ; RNA Transport ; RNA, Messenger - biosynthesis ; siRNA ; swallowing</subject><ispartof>Human molecular genetics, 2010-03, Vol.19 (6), p.1058-1065</ispartof><rights>The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org 2010</rights><rights>2015 INIST-CNRS</rights><rights>The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-44d3f31d837ef3cc862a2e313e4b5008debad8505e9b9fa5ce86f717af59ec5a3</citedby><cites>FETCH-LOGICAL-c573t-44d3f31d837ef3cc862a2e313e4b5008debad8505e9b9fa5ce86f717af59ec5a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22472882$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20035013$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Apponi, Luciano H.</creatorcontrib><creatorcontrib>Leung, Sara W.</creatorcontrib><creatorcontrib>Williams, Kathryn R.</creatorcontrib><creatorcontrib>Valentini, Sandro R.</creatorcontrib><creatorcontrib>Corbett, Anita H.</creatorcontrib><creatorcontrib>Pavlath, Grace K.</creatorcontrib><title>Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><description>The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed protein that plays a critical role in polyadenylation. Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by eyelid drooping, difficulty in swallowing and weakness in the proximal limb muscles. Although significant data from in vitro biochemical assays define the function of PABPN1 in control of poly(A) tail length, little is known about the role of PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells and specifically in cells affected in OPMD, we examined the effects of PABPN1 depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and limb muscles. PABPN1 knockdown significantly decreased cell proliferation and myoblast differentiation during myogenesis in vitro. At the molecular level, PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails, demonstrating the cellular function of PABPN1 in polyadenylation control in a mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from the nucleus. Together, these experiments demonstrate that PABPN1 plays an essential role in myoblast proliferation and differentiation, suggesting that it is required for muscle regeneration and maintenance in vivo.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Differentiation</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Proliferation</subject><subject>Data processing</subject><subject>Differentiation</subject><subject>Eyelid</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Limbs</subject><subject>Mammalian cells</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Molecular and cellular biology</subject><subject>mRNA</subject><subject>Muscle Development</subject><subject>Muscular dystrophy</subject><subject>Myoblasts</subject><subject>Myoblasts - cytology</subject><subject>Myoblasts - metabolism</subject><subject>myogenesis</subject><subject>N-Terminus</subject><subject>Nuclei</subject><subject>Pharynx</subject><subject>Poly A - metabolism</subject><subject>poly(A)-binding protein</subject><subject>Poly(A)-Binding Protein I - metabolism</subject><subject>Poly(A)-Binding Protein II - metabolism</subject><subject>Polyadenylation</subject><subject>polyalanine</subject><subject>RNA Transport</subject><subject>RNA, Messenger - biosynthesis</subject><subject>siRNA</subject><subject>swallowing</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0VuL1DAYBuAiijuu3vgDJDfiAermnPZGGAZ1hEFRVpS5CWnyZTbapjVpxfn3VmZ2Vm_0KvDl4c3hLYqHBL8guGYXV93uwrlByPpWsSBc4pLiit0uFriWvJQ1lmfFvZy_YkwkZ-pucUYxZgITtii2mz5n1HsUJ9uCSWjo2_3T5bOyCdGFuEND6kcIERFkzZQhIwce7JjRPOv2_Q4i5JCRiQ51H98tUROuZ_eLO960GR4c1_Pi0-tXl6t1uXn_5u1quSmtUGwsOXfMM-IqpsAzaytJDQVGGPBGYFw5aIyrBBZQN7U3wkIlvSLKeFGDFYadFy8PucPUdOAsxDGZVg8pdCbtdW-C_nsnhiu9639oWjFc0XoOeHIMSP33CfKou5AttK2J0E9ZKy6JpJTT_0vGqKCSy1k-P0ib5g9O4E_3IVj_bk3PrelDazN-9OcLTvS6phk8PgKTrWl9MtGGfOMoV7Sq6I3rp-HfB5YHF_IIP0_SpG9aKqaEXn_Z6pW6ZJ_Vh7Xesl-yer11</recordid><startdate>20100315</startdate><enddate>20100315</enddate><creator>Apponi, Luciano H.</creator><creator>Leung, Sara W.</creator><creator>Williams, Kathryn R.</creator><creator>Valentini, Sandro R.</creator><creator>Corbett, Anita H.</creator><creator>Pavlath, Grace K.</creator><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20100315</creationdate><title>Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis</title><author>Apponi, Luciano H. ; Leung, Sara W. ; Williams, Kathryn R. ; Valentini, Sandro R. ; Corbett, Anita H. ; Pavlath, Grace K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-44d3f31d837ef3cc862a2e313e4b5008debad8505e9b9fa5ce86f717af59ec5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Differentiation</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Proliferation</topic><topic>Data processing</topic><topic>Differentiation</topic><topic>Eyelid</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Limbs</topic><topic>Mammalian cells</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Molecular and cellular biology</topic><topic>mRNA</topic><topic>Muscle Development</topic><topic>Muscular dystrophy</topic><topic>Myoblasts</topic><topic>Myoblasts - cytology</topic><topic>Myoblasts - metabolism</topic><topic>myogenesis</topic><topic>N-Terminus</topic><topic>Nuclei</topic><topic>Pharynx</topic><topic>Poly A - metabolism</topic><topic>poly(A)-binding protein</topic><topic>Poly(A)-Binding Protein I - metabolism</topic><topic>Poly(A)-Binding Protein II - metabolism</topic><topic>Polyadenylation</topic><topic>polyalanine</topic><topic>RNA Transport</topic><topic>RNA, Messenger - biosynthesis</topic><topic>siRNA</topic><topic>swallowing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Apponi, Luciano H.</creatorcontrib><creatorcontrib>Leung, Sara W.</creatorcontrib><creatorcontrib>Williams, Kathryn R.</creatorcontrib><creatorcontrib>Valentini, Sandro R.</creatorcontrib><creatorcontrib>Corbett, Anita H.</creatorcontrib><creatorcontrib>Pavlath, Grace K.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</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>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</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>Apponi, Luciano H.</au><au>Leung, Sara W.</au><au>Williams, Kathryn R.</au><au>Valentini, Sandro R.</au><au>Corbett, Anita H.</au><au>Pavlath, Grace K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2010-03-15</date><risdate>2010</risdate><volume>19</volume><issue>6</issue><spage>1058</spage><epage>1065</epage><pages>1058-1065</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><abstract>The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed protein that plays a critical role in polyadenylation. Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by eyelid drooping, difficulty in swallowing and weakness in the proximal limb muscles. Although significant data from in vitro biochemical assays define the function of PABPN1 in control of poly(A) tail length, little is known about the role of PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells and specifically in cells affected in OPMD, we examined the effects of PABPN1 depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and limb muscles. PABPN1 knockdown significantly decreased cell proliferation and myoblast differentiation during myogenesis in vitro. At the molecular level, PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails, demonstrating the cellular function of PABPN1 in polyadenylation control in a mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from the nucleus. Together, these experiments demonstrate that PABPN1 plays an essential role in myoblast proliferation and differentiation, suggesting that it is required for muscle regeneration and maintenance in vivo.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>20035013</pmid><doi>10.1093/hmg/ddp569</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Biological and medical sciences Cell Differentiation Cell Nucleus - metabolism Cell Proliferation Data processing Differentiation Eyelid Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Limbs Mammalian cells Mice Mice, Inbred BALB C Molecular and cellular biology mRNA Muscle Development Muscular dystrophy Myoblasts Myoblasts - cytology Myoblasts - metabolism myogenesis N-Terminus Nuclei Pharynx Poly A - metabolism poly(A)-binding protein Poly(A)-Binding Protein I - metabolism Poly(A)-Binding Protein II - metabolism Polyadenylation polyalanine RNA Transport RNA, Messenger - biosynthesis siRNA swallowing |
| title | Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis |
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