{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:56:05Z","timestamp":1791860165129,"version":"4.3.4"},"reference-count":83,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Center for Cardiovascular Research (DZHK)","award":["B19-006_SE"],"award-info":[{"award-number":["B19-006_SE"]}]},{"name":"German Center for Cardiovascular Research (DZHK)","award":["B18-004_SE"],"award-info":[{"award-number":["B18-004_SE"]}]},{"name":"German Center for Cardiovascular Research (DZHK)","award":["FKZ 81Z0710102"],"award-info":[{"award-number":["FKZ 81Z0710102"]}]},{"name":"German Center for Cardiovascular Research (DZHK)","award":["FKZ 01ZX1906B"],"award-info":[{"award-number":["FKZ 01ZX1906B"]}]},{"name":"German Center of Cardiovascular Disease","award":["B19-006_SE"],"award-info":[{"award-number":["B19-006_SE"]}]},{"name":"German Center of Cardiovascular Disease","award":["B18-004_SE"],"award-info":[{"award-number":["B18-004_SE"]}]},{"name":"German Center of Cardiovascular Disease","award":["FKZ 81Z0710102"],"award-info":[{"award-number":["FKZ 81Z0710102"]}]},{"name":"German Center of Cardiovascular Disease","award":["FKZ 01ZX1906B"],"award-info":[{"award-number":["FKZ 01ZX1906B"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["B19-006_SE"],"award-info":[{"award-number":["B19-006_SE"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["B18-004_SE"],"award-info":[{"award-number":["B18-004_SE"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["FKZ 81Z0710102"],"award-info":[{"award-number":["FKZ 81Z0710102"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["FKZ 01ZX1906B"],"award-info":[{"award-number":["FKZ 01ZX1906B"]}]},{"name":"Berlin Institute of Health (BIH)","award":["B19-006_SE"],"award-info":[{"award-number":["B19-006_SE"]}]},{"name":"Berlin Institute of Health (BIH)","award":["B18-004_SE"],"award-info":[{"award-number":["B18-004_SE"]}]},{"name":"Berlin Institute of Health (BIH)","award":["FKZ 81Z0710102"],"award-info":[{"award-number":["FKZ 81Z0710102"]}]},{"name":"Berlin Institute of Health (BIH)","award":["FKZ 01ZX1906B"],"award-info":[{"award-number":["FKZ 01ZX1906B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The evolutionary conserved NEAT1-MALAT1 gene cluster generates large noncoding transcripts remaining nuclear, while tRNA-like transcripts (mascRNA, menRNA) enzymatically generated from these precursors translocate to the cytosol. Whereas functions have been assigned to the nuclear transcripts, data on biological functions of the small cytosolic transcripts are sparse. We previously found NEAT1\u2212\/\u2212 and MALAT1\u2212\/\u2212 mice to display massive atherosclerosis and vascular inflammation. Here, employing selective targeted disruption of menRNA or mascRNA, we investigate the tRNA-like molecules as critical components of innate immunity. CRISPR-generated human \u0394mascRNA and \u0394menRNA monocytes\/macrophages display defective innate immune sensing, loss of cytokine control, imbalance of growth\/angiogenic factor expression impacting upon angiogenesis, and altered cell\u2013cell interaction systems. Antiviral response, foam cell formation\/oxLDL uptake, and M1\/M2 polarization are defective in \u0394mascRNA\/\u0394menRNA macrophages, defining first biological functions of menRNA and describing new functions of mascRNA. menRNA and mascRNA represent novel components of innate immunity arising from the noncoding genome. They appear as prototypes of a new class of noncoding RNAs distinct from others (miRNAs, siRNAs) by biosynthetic pathway and intracellular kinetics. Their NEAT1-MALAT1 region of origin appears as archetype of a functionally highly integrated RNA processing system.<\/jats:p>","DOI":"10.3390\/cells11243970","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T02:50:51Z","timestamp":1670554251000},"page":"3970","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions"],"prefix":"10.3390","volume":"11","author":[{"given":"Martina","family":"Gast","sequence":"first","affiliation":[{"name":"Department of Cardiology, Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 12200 Berlin, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Site Berlin, 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4738-2558","authenticated-orcid":false,"given":"Vanasa","family":"Nageswaran","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 12200 Berlin, Germany"},{"name":"Institute for Chemistry and Biochemistry, Freie Universit\u00e4t Berlin, 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-4627","authenticated-orcid":false,"given":"Andreas W.","family":"Kuss","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Tzvetkova","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"Institute of Bioinformatics, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana H.","family":"Mochmann","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-9149","authenticated-orcid":false,"given":"Pegah Ramezani","family":"Rad","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3553-4315","authenticated-orcid":false,"given":"Stefan","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Site Greifswald, 17487 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Simm","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Zeller","sequence":"additional","affiliation":[{"name":"University Center of Cardiovascular Science, University Heart and Vascular Center, 20246 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Site Hamburg\/L\u00fcbeck\/Kiel, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Voelzke","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Site Greifswald, 17487 Greifswald, Germany"},{"name":"Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6359-8797","authenticated-orcid":false,"given":"Wolfgang","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Site Greifswald, 17487 Greifswald, Germany"},{"name":"Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5689-3448","authenticated-orcid":false,"given":"Uwe","family":"V\u00f6lker","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Site Greifswald, 17487 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan B.","family":"Felix","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Site Greifswald, 17487 Greifswald, Germany"},{"name":"Department of Cardiology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7471-475X","authenticated-orcid":false,"given":"Marcus","family":"D\u00f6rr","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Site Greifswald, 17487 Greifswald, Germany"},{"name":"Department of Cardiology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-5248","authenticated-orcid":false,"given":"Antje","family":"Beling","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Site Berlin, 12200 Berlin, Germany"},{"name":"Institute for Biochemistry, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 10178 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), 10178 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4953-601X","authenticated-orcid":false,"given":"Carsten","family":"Skurk","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 12200 Berlin, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Site Berlin, 12200 Berlin, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-6634","authenticated-orcid":false,"given":"Wolfgang","family":"Poller","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 12200 Berlin, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Site Berlin, 12200 Berlin, Germany"},{"name":"Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1093\/cvr\/cvz085","article-title":"Long noncoding RNA NEAT1 modulates immune cell functions and is suppressed in early onset myocardial infarction patients","volume":"115","author":"Gast","year":"2019","journal-title":"Cardiovasc. 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