UBQLN1 deficiency mediates telomere shortening and IPF through interacting with RPA1
Premature telomere shortening is a known factor correlated to idiopathic pulmonary fibrosis (IPF) occurrence, which is a chronic, progressive, age-related disease with high mortality. The etiology of IPF is still unknown. Here, we found that UBQLN1 plays a key role in telomere length maintenance and...
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| Veröffentlicht in: | PLoS genetics 2023-07, Vol.19 (7), p.e1010856-e1010856 |
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| creator | Zhou, Haoxian Xie, Chen Xie, Yujie He, Yunru Chen, Yanlian Zhang, Canfeng Zhang, Yan Zhao, Yong Liu, Haiying |
| description | Premature telomere shortening is a known factor correlated to idiopathic pulmonary fibrosis (IPF) occurrence, which is a chronic, progressive, age-related disease with high mortality. The etiology of IPF is still unknown. Here, we found that UBQLN1 plays a key role in telomere length maintenance and is potentially relevant to IPF. UBQLN1 involves in DNA replication by interacting with RPA1 and shuttling it off from the replication fork. The deficiency of UBQLN1 retains RPA1 at replication fork, hinders replication and thus causes cell cycle arrest and genome instability. Especially at telomere regions of the genome, where more endogenous replication stress exists because of G rich sequences, UBQLN1 depletion leads to rapid telomere shortening in HeLa cells. It revealed that UBQLN1 depletion also shortens telomere length at mouse lung and accelerates mouse lung fibrosis. In addition, the UBQLN1 expression level in IPF patients is downregulated and correlated to poor prognosis. Altogether, these results uncover a new role of UBQLN1 in ensuring DNA replication and maintaining telomere stability, which may shed light on IPF pathogenesis and prevention. |
| doi_str_mv | 10.1371/journal.pgen.1010856 |
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The etiology of IPF is still unknown. Here, we found that UBQLN1 plays a key role in telomere length maintenance and is potentially relevant to IPF. UBQLN1 involves in DNA replication by interacting with RPA1 and shuttling it off from the replication fork. The deficiency of UBQLN1 retains RPA1 at replication fork, hinders replication and thus causes cell cycle arrest and genome instability. Especially at telomere regions of the genome, where more endogenous replication stress exists because of G rich sequences, UBQLN1 depletion leads to rapid telomere shortening in HeLa cells. It revealed that UBQLN1 depletion also shortens telomere length at mouse lung and accelerates mouse lung fibrosis. In addition, the UBQLN1 expression level in IPF patients is downregulated and correlated to poor prognosis. Altogether, these results uncover a new role of UBQLN1 in ensuring DNA replication and maintaining telomere stability, which may shed light on IPF pathogenesis and prevention.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1010856</identifier><identifier>PMID: 37463174</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Alzheimer's disease ; Analysis ; Biology and Life Sciences ; Cell cycle ; Cell division ; DNA biosynthesis ; DNA damage ; DNA polymerase ; DNA replication ; Fibrosis ; Gene expression ; Genetic aspects ; Genomes ; Genomic instability ; Genomics ; Health aspects ; Identification and classification ; Lung diseases ; Properties ; Proteins ; Pulmonary fibrosis ; Replication ; Research and Analysis Methods ; Stem cells ; Telomerase ; Telomeres ; Ubiquitin ; Yeast</subject><ispartof>PLoS genetics, 2023-07, Vol.19 (7), p.e1010856-e1010856</ispartof><rights>Copyright: © 2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Zhou et al 2023 Zhou et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c661t-79fcbfcf83564c1b4e1f4c714cd3ef4f43d520b9abffd5bd5300f599e5bd67df3</citedby><cites>FETCH-LOGICAL-c661t-79fcbfcf83564c1b4e1f4c714cd3ef4f43d520b9abffd5bd5300f599e5bd67df3</cites><orcidid>0000-0002-0173-3375</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381042/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381042/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2929,23870,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37463174$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhou, Jin-Qiu</contributor><creatorcontrib>Zhou, Haoxian</creatorcontrib><creatorcontrib>Xie, Chen</creatorcontrib><creatorcontrib>Xie, Yujie</creatorcontrib><creatorcontrib>He, Yunru</creatorcontrib><creatorcontrib>Chen, Yanlian</creatorcontrib><creatorcontrib>Zhang, Canfeng</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Zhao, Yong</creatorcontrib><creatorcontrib>Liu, Haiying</creatorcontrib><title>UBQLN1 deficiency mediates telomere shortening and IPF through interacting with RPA1</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Premature telomere shortening is a known factor correlated to idiopathic pulmonary fibrosis (IPF) occurrence, which is a chronic, progressive, age-related disease with high mortality. The etiology of IPF is still unknown. Here, we found that UBQLN1 plays a key role in telomere length maintenance and is potentially relevant to IPF. UBQLN1 involves in DNA replication by interacting with RPA1 and shuttling it off from the replication fork. The deficiency of UBQLN1 retains RPA1 at replication fork, hinders replication and thus causes cell cycle arrest and genome instability. Especially at telomere regions of the genome, where more endogenous replication stress exists because of G rich sequences, UBQLN1 depletion leads to rapid telomere shortening in HeLa cells. It revealed that UBQLN1 depletion also shortens telomere length at mouse lung and accelerates mouse lung fibrosis. In addition, the UBQLN1 expression level in IPF patients is downregulated and correlated to poor prognosis. Altogether, these results uncover a new role of UBQLN1 in ensuring DNA replication and maintaining telomere stability, which may shed light on IPF pathogenesis and prevention.</description><subject>Age</subject><subject>Alzheimer's disease</subject><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Cell cycle</subject><subject>Cell division</subject><subject>DNA biosynthesis</subject><subject>DNA damage</subject><subject>DNA polymerase</subject><subject>DNA replication</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genomic instability</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>Identification and classification</subject><subject>Lung diseases</subject><subject>Properties</subject><subject>Proteins</subject><subject>Pulmonary fibrosis</subject><subject>Replication</subject><subject>Research and Analysis Methods</subject><subject>Stem 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IPF through interacting with RPA1</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2023-07-18</date><risdate>2023</risdate><volume>19</volume><issue>7</issue><spage>e1010856</spage><epage>e1010856</epage><pages>e1010856-e1010856</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Premature telomere shortening is a known factor correlated to idiopathic pulmonary fibrosis (IPF) occurrence, which is a chronic, progressive, age-related disease with high mortality. The etiology of IPF is still unknown. Here, we found that UBQLN1 plays a key role in telomere length maintenance and is potentially relevant to IPF. UBQLN1 involves in DNA replication by interacting with RPA1 and shuttling it off from the replication fork. The deficiency of UBQLN1 retains RPA1 at replication fork, hinders replication and thus causes cell cycle arrest and genome instability. Especially at telomere regions of the genome, where more endogenous replication stress exists because of G rich sequences, UBQLN1 depletion leads to rapid telomere shortening in HeLa cells. It revealed that UBQLN1 depletion also shortens telomere length at mouse lung and accelerates mouse lung fibrosis. In addition, the UBQLN1 expression level in IPF patients is downregulated and correlated to poor prognosis. Altogether, these results uncover a new role of UBQLN1 in ensuring DNA replication and maintaining telomere stability, which may shed light on IPF pathogenesis and prevention.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37463174</pmid><doi>10.1371/journal.pgen.1010856</doi><tpages>e1010856</tpages><orcidid>https://orcid.org/0000-0002-0173-3375</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Alzheimer's disease Analysis Biology and Life Sciences Cell cycle Cell division DNA biosynthesis DNA damage DNA polymerase DNA replication Fibrosis Gene expression Genetic aspects Genomes Genomic instability Genomics Health aspects Identification and classification Lung diseases Properties Proteins Pulmonary fibrosis Replication Research and Analysis Methods Stem cells Telomerase Telomeres Ubiquitin Yeast |
| title | UBQLN1 deficiency mediates telomere shortening and IPF through interacting with RPA1 |
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