The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles
PEG10 is a retroelement-derived Mart-family gene that is necessary for placentation and has been implicated in neurological disease. PEG10 resembles both retrotransposon and retroviral proteins and forms virus-like particles (VLPs) that can be purified using iodixanol ultracentrifugation. It is hypo...
Gespeichert in:
| Veröffentlicht in: | PloS one 2024-12, Vol.19 (12), p.e0310946 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 12 |
| container_start_page | e0310946 |
| container_title | PloS one |
| container_volume | 19 |
| creator | Campodonico, Will Mohan, Harihar M Huynh, Phuoc T Black, Holly H Lau, Cristina I Paulson, Henry L Sharkey, Lisa M Whiteley, Alexandra M |
| description | PEG10 is a retroelement-derived Mart-family gene that is necessary for placentation and has been implicated in neurological disease. PEG10 resembles both retrotransposon and retroviral proteins and forms virus-like particles (VLPs) that can be purified using iodixanol ultracentrifugation. It is hypothesized that formation of VLPs is crucial to the biological roles of PEG10 in reproduction and neurological health. Here, we describe the regulation of PEG10 VLP formation and release in human cells with a role for the related Mart gene RTL8. RTL8 resembles a truncated form of PEG10 that shares homology with the N-terminal gag-like capsid domain. Alone, RTL8 is unable to form VLPs, but was incorporated into PEG10-derived particles. RTL8 co-expression decreased the abundance of PEG10 VLPs and increased intracellular levels of PEG10, suggesting a model where RTL8 inhibits PEG10 VLP formation or release. Consistent with this model, RTL8 bound to the N-terminal domain of PEG10 capsid, and modulation of RTL8 influenced PEG10-derived VLP abundance in naturally producing cells. RTL8 is broadly expressed in many of the same tissues as PEG10, including in human brain. Taken together, these results describe a novel antagonistic relationship between two human retroelement-derived genes and have implications for our understanding of PEG10 biology and disease. |
| doi_str_mv | 10.1371/journal.pone.0310946 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_3150324329</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A821837585</galeid><doaj_id>oai_doaj_org_article_35aa10ba17e3457493236aac31ccb7d9</doaj_id><sourcerecordid>A821837585</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4876-5ab363ee0456101432c1361cb8df1d2ca17267f167ce1cdb7c7444ad3d83f9f43</originalsourceid><addsrcrecordid>eNqNklFv0zAQxyMEYmPwDRBEQkLwkOKLHTt5QtO0jUqVhkbh1bo4TuqSxp2dTMCnx12zqUF7QH6wdf7d_3znfxS9BjIDKuDT2g6uw3a2tZ2eEQqkYPxJdAwFTROeEvr04HwUvfB-TUhGc86fR0e0ECKjWXEcXSxXOm6wSVrzMxx0p-Pr5SKPseuxsZ35o3389fwSSLLRlcFeV_GtcYOP7_gtut6oVvuX0bMaW69fjftJ9P3ifHn2JVlcXc7PTheJYrngSYYl5VRrwjIOBBhNFVAOqsyrGqpUIYiUixq4UBpUVQolGGNY0SqndVEzehK93etuW-vlOAIvKWSEpkGuCMR8T1QW13LrzAbdb2nRyLuAdY0cHy1phgikDEU1ZZlgYVqUIyoKSpWi2ml9HqsNZWhf6a532E5EpzedWcnG3koAnjOe8qDwYVRw9mbQvpcb45VuW-y0HXYP56RIiYA8oO_-QR9vb6QaDB2YrrahsNqJytM8DTIiy7NAzR6hwqr0xqhgmNqE-CTh4yQhML3-1Tc4eC_n367_n736MWXfH7ArjW2_8rYdemM7PwXZHlTOeu90_TBlIHLn9_tpyJ3f5ej3kPbm8Iceku4NTv8C1Tr3uQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3150324329</pqid></control><display><type>article</type><title>The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Campodonico, Will ; Mohan, Harihar M ; Huynh, Phuoc T ; Black, Holly H ; Lau, Cristina I ; Paulson, Henry L ; Sharkey, Lisa M ; Whiteley, Alexandra M</creator><creatorcontrib>Campodonico, Will ; Mohan, Harihar M ; Huynh, Phuoc T ; Black, Holly H ; Lau, Cristina I ; Paulson, Henry L ; Sharkey, Lisa M ; Whiteley, Alexandra M</creatorcontrib><description>PEG10 is a retroelement-derived Mart-family gene that is necessary for placentation and has been implicated in neurological disease. PEG10 resembles both retrotransposon and retroviral proteins and forms virus-like particles (VLPs) that can be purified using iodixanol ultracentrifugation. It is hypothesized that formation of VLPs is crucial to the biological roles of PEG10 in reproduction and neurological health. Here, we describe the regulation of PEG10 VLP formation and release in human cells with a role for the related Mart gene RTL8. RTL8 resembles a truncated form of PEG10 that shares homology with the N-terminal gag-like capsid domain. Alone, RTL8 is unable to form VLPs, but was incorporated into PEG10-derived particles. RTL8 co-expression decreased the abundance of PEG10 VLPs and increased intracellular levels of PEG10, suggesting a model where RTL8 inhibits PEG10 VLP formation or release. Consistent with this model, RTL8 bound to the N-terminal domain of PEG10 capsid, and modulation of RTL8 influenced PEG10-derived VLP abundance in naturally producing cells. RTL8 is broadly expressed in many of the same tissues as PEG10, including in human brain. Taken together, these results describe a novel antagonistic relationship between two human retroelement-derived genes and have implications for our understanding of PEG10 biology and disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0310946</identifier><identifier>PMID: 39775359</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Apoptosis Regulatory Proteins ; Biochemistry ; Biological effects ; Biology and Life Sciences ; Capsid Proteins - genetics ; Capsid Proteins - metabolism ; Care and treatment ; Cloning ; Complications and side effects ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; E coli ; Gag protein ; Gene expression ; Genes ; HEK293 Cells ; Homology ; Humans ; Intracellular levels ; Neurological diseases ; Penicillin ; Pregnancy Proteins - genetics ; Pregnancy Proteins - metabolism ; Proteins ; Research and Analysis Methods ; Retrovirus infections ; Risk factors ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; Ultracentrifugation ; Vaccines ; Virion - genetics ; Virion - metabolism ; Virus-like particles</subject><ispartof>PloS one, 2024-12, Vol.19 (12), p.e0310946</ispartof><rights>Copyright: © 2024 Campodonico 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 2024 Public Library of Science</rights><rights>2024 Campodonico 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>2024 Campodonico et al 2024 Campodonico et al</rights><rights>2024 Campodonico 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4876-5ab363ee0456101432c1361cb8df1d2ca17267f167ce1cdb7c7444ad3d83f9f43</cites><orcidid>0000-0002-4144-7605 ; 0000-0002-9098-5266 ; 0000-0002-2288-3970</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/PMC11684626/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684626/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39775359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Campodonico, Will</creatorcontrib><creatorcontrib>Mohan, Harihar M</creatorcontrib><creatorcontrib>Huynh, Phuoc T</creatorcontrib><creatorcontrib>Black, Holly H</creatorcontrib><creatorcontrib>Lau, Cristina I</creatorcontrib><creatorcontrib>Paulson, Henry L</creatorcontrib><creatorcontrib>Sharkey, Lisa M</creatorcontrib><creatorcontrib>Whiteley, Alexandra M</creatorcontrib><title>The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>PEG10 is a retroelement-derived Mart-family gene that is necessary for placentation and has been implicated in neurological disease. PEG10 resembles both retrotransposon and retroviral proteins and forms virus-like particles (VLPs) that can be purified using iodixanol ultracentrifugation. It is hypothesized that formation of VLPs is crucial to the biological roles of PEG10 in reproduction and neurological health. Here, we describe the regulation of PEG10 VLP formation and release in human cells with a role for the related Mart gene RTL8. RTL8 resembles a truncated form of PEG10 that shares homology with the N-terminal gag-like capsid domain. Alone, RTL8 is unable to form VLPs, but was incorporated into PEG10-derived particles. RTL8 co-expression decreased the abundance of PEG10 VLPs and increased intracellular levels of PEG10, suggesting a model where RTL8 inhibits PEG10 VLP formation or release. Consistent with this model, RTL8 bound to the N-terminal domain of PEG10 capsid, and modulation of RTL8 influenced PEG10-derived VLP abundance in naturally producing cells. RTL8 is broadly expressed in many of the same tissues as PEG10, including in human brain. Taken together, these results describe a novel antagonistic relationship between two human retroelement-derived genes and have implications for our understanding of PEG10 biology and disease.</description><subject>Analysis</subject><subject>Apoptosis Regulatory Proteins</subject><subject>Biochemistry</subject><subject>Biological effects</subject><subject>Biology and Life Sciences</subject><subject>Capsid Proteins - genetics</subject><subject>Capsid Proteins - metabolism</subject><subject>Care and treatment</subject><subject>Cloning</subject><subject>Complications and side effects</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>E coli</subject><subject>Gag protein</subject><subject>Gene expression</subject><subject>Genes</subject><subject>HEK293 Cells</subject><subject>Homology</subject><subject>Humans</subject><subject>Intracellular levels</subject><subject>Neurological diseases</subject><subject>Penicillin</subject><subject>Pregnancy Proteins - genetics</subject><subject>Pregnancy Proteins - metabolism</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Retrovirus infections</subject><subject>Risk factors</subject><subject>RNA-Binding Proteins - genetics</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Ultracentrifugation</subject><subject>Vaccines</subject><subject>Virion - genetics</subject><subject>Virion - metabolism</subject><subject>Virus-like particles</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNklFv0zAQxyMEYmPwDRBEQkLwkOKLHTt5QtO0jUqVhkbh1bo4TuqSxp2dTMCnx12zqUF7QH6wdf7d_3znfxS9BjIDKuDT2g6uw3a2tZ2eEQqkYPxJdAwFTROeEvr04HwUvfB-TUhGc86fR0e0ECKjWXEcXSxXOm6wSVrzMxx0p-Pr5SKPseuxsZ35o3389fwSSLLRlcFeV_GtcYOP7_gtut6oVvuX0bMaW69fjftJ9P3ifHn2JVlcXc7PTheJYrngSYYl5VRrwjIOBBhNFVAOqsyrGqpUIYiUixq4UBpUVQolGGNY0SqndVEzehK93etuW-vlOAIvKWSEpkGuCMR8T1QW13LrzAbdb2nRyLuAdY0cHy1phgikDEU1ZZlgYVqUIyoKSpWi2ml9HqsNZWhf6a532E5EpzedWcnG3koAnjOe8qDwYVRw9mbQvpcb45VuW-y0HXYP56RIiYA8oO_-QR9vb6QaDB2YrrahsNqJytM8DTIiy7NAzR6hwqr0xqhgmNqE-CTh4yQhML3-1Tc4eC_n367_n736MWXfH7ArjW2_8rYdemM7PwXZHlTOeu90_TBlIHLn9_tpyJ3f5ej3kPbm8Iceku4NTv8C1Tr3uQ</recordid><startdate>20241230</startdate><enddate>20241230</enddate><creator>Campodonico, Will</creator><creator>Mohan, Harihar M</creator><creator>Huynh, Phuoc T</creator><creator>Black, Holly H</creator><creator>Lau, Cristina I</creator><creator>Paulson, Henry L</creator><creator>Sharkey, Lisa M</creator><creator>Whiteley, Alexandra M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4144-7605</orcidid><orcidid>https://orcid.org/0000-0002-9098-5266</orcidid><orcidid>https://orcid.org/0000-0002-2288-3970</orcidid></search><sort><creationdate>20241230</creationdate><title>The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles</title><author>Campodonico, Will ; Mohan, Harihar M ; Huynh, Phuoc T ; Black, Holly H ; Lau, Cristina I ; Paulson, Henry L ; Sharkey, Lisa M ; Whiteley, Alexandra M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4876-5ab363ee0456101432c1361cb8df1d2ca17267f167ce1cdb7c7444ad3d83f9f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Analysis</topic><topic>Apoptosis Regulatory Proteins</topic><topic>Biochemistry</topic><topic>Biological effects</topic><topic>Biology and Life Sciences</topic><topic>Capsid Proteins - genetics</topic><topic>Capsid Proteins - metabolism</topic><topic>Care and treatment</topic><topic>Cloning</topic><topic>Complications and side effects</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>E coli</topic><topic>Gag protein</topic><topic>Gene expression</topic><topic>Genes</topic><topic>HEK293 Cells</topic><topic>Homology</topic><topic>Humans</topic><topic>Intracellular levels</topic><topic>Neurological diseases</topic><topic>Penicillin</topic><topic>Pregnancy Proteins - genetics</topic><topic>Pregnancy Proteins - metabolism</topic><topic>Proteins</topic><topic>Research and Analysis Methods</topic><topic>Retrovirus infections</topic><topic>Risk factors</topic><topic>RNA-Binding Proteins - genetics</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Ultracentrifugation</topic><topic>Vaccines</topic><topic>Virion - genetics</topic><topic>Virion - metabolism</topic><topic>Virus-like particles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Campodonico, Will</creatorcontrib><creatorcontrib>Mohan, Harihar M</creatorcontrib><creatorcontrib>Huynh, Phuoc T</creatorcontrib><creatorcontrib>Black, Holly H</creatorcontrib><creatorcontrib>Lau, Cristina I</creatorcontrib><creatorcontrib>Paulson, Henry L</creatorcontrib><creatorcontrib>Sharkey, Lisa M</creatorcontrib><creatorcontrib>Whiteley, Alexandra M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Campodonico, Will</au><au>Mohan, Harihar M</au><au>Huynh, Phuoc T</au><au>Black, Holly H</au><au>Lau, Cristina I</au><au>Paulson, Henry L</au><au>Sharkey, Lisa M</au><au>Whiteley, Alexandra M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024-12-30</date><risdate>2024</risdate><volume>19</volume><issue>12</issue><spage>e0310946</spage><pages>e0310946-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>PEG10 is a retroelement-derived Mart-family gene that is necessary for placentation and has been implicated in neurological disease. PEG10 resembles both retrotransposon and retroviral proteins and forms virus-like particles (VLPs) that can be purified using iodixanol ultracentrifugation. It is hypothesized that formation of VLPs is crucial to the biological roles of PEG10 in reproduction and neurological health. Here, we describe the regulation of PEG10 VLP formation and release in human cells with a role for the related Mart gene RTL8. RTL8 resembles a truncated form of PEG10 that shares homology with the N-terminal gag-like capsid domain. Alone, RTL8 is unable to form VLPs, but was incorporated into PEG10-derived particles. RTL8 co-expression decreased the abundance of PEG10 VLPs and increased intracellular levels of PEG10, suggesting a model where RTL8 inhibits PEG10 VLP formation or release. Consistent with this model, RTL8 bound to the N-terminal domain of PEG10 capsid, and modulation of RTL8 influenced PEG10-derived VLP abundance in naturally producing cells. RTL8 is broadly expressed in many of the same tissues as PEG10, including in human brain. Taken together, these results describe a novel antagonistic relationship between two human retroelement-derived genes and have implications for our understanding of PEG10 biology and disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39775359</pmid><doi>10.1371/journal.pone.0310946</doi><tpages>e0310946</tpages><orcidid>https://orcid.org/0000-0002-4144-7605</orcidid><orcidid>https://orcid.org/0000-0002-9098-5266</orcidid><orcidid>https://orcid.org/0000-0002-2288-3970</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2024-12, Vol.19 (12), p.e0310946 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_3150324329 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Apoptosis Regulatory Proteins Biochemistry Biological effects Biology and Life Sciences Capsid Proteins - genetics Capsid Proteins - metabolism Care and treatment Cloning Complications and side effects DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism E coli Gag protein Gene expression Genes HEK293 Cells Homology Humans Intracellular levels Neurological diseases Penicillin Pregnancy Proteins - genetics Pregnancy Proteins - metabolism Proteins Research and Analysis Methods Retrovirus infections Risk factors RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Ultracentrifugation Vaccines Virion - genetics Virion - metabolism Virus-like particles |
| title | The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T19%3A19%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20gag-like%20gene%20RTL8%20antagonizes%20PEG10-mediated%20virus%20like%20particles&rft.jtitle=PloS%20one&rft.au=Campodonico,%20Will&rft.date=2024-12-30&rft.volume=19&rft.issue=12&rft.spage=e0310946&rft.pages=e0310946-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0310946&rft_dat=%3Cgale_plos_%3EA821837585%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3150324329&rft_id=info:pmid/39775359&rft_galeid=A821837585&rft_doaj_id=oai_doaj_org_article_35aa10ba17e3457493236aac31ccb7d9&rfr_iscdi=true |