{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:31:58Z","timestamp":1781613118965,"version":"3.54.5"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T00:00:00Z","timestamp":1684540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH\/NHLBI","doi-asserted-by":"publisher","award":["R01HL155905"],"award-info":[{"award-number":["R01HL155905"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH\/NHLBI","doi-asserted-by":"publisher","award":["R01HL140472"],"award-info":[{"award-number":["R01HL140472"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH\/NHLBI","doi-asserted-by":"publisher","award":["F32HL160099"],"award-info":[{"award-number":["F32HL160099"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>The PAF1 complex component Rtf1 is an RNA Polymerase II-interacting transcription regulatory protein that promotes transcription elongation and the co-transcriptional monoubiquitination of histone 2B. Rtf1 plays an essential role in the specification of cardiac progenitors from the lateral plate mesoderm during early embryogenesis, but its requirement in mature cardiac cells is unknown. Here, we investigate the importance of Rtf1 in neonatal and adult cardiomyocytes using knockdown and knockout approaches. We demonstrate that loss of Rtf1 activity in neonatal cardiomyocytes disrupts cell morphology and results in a breakdown of sarcomeres. Similarly, Rtf1 ablation in mature cardiomyocytes of the adult mouse heart leads to myofibril disorganization, disrupted cell\u2013cell junctions, fibrosis, and systolic dysfunction. Rtf1 knockout hearts eventually fail and exhibit structural and gene expression defects resembling dilated cardiomyopathy. Intriguingly, we observed that loss of Rtf1 activity causes a rapid change in the expression of key cardiac structural and functional genes in both neonatal and adult cardiomyocytes, suggesting that Rtf1 is continuously required to support expression of the cardiac gene program.<\/jats:p>","DOI":"10.3390\/jcdd10050221","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T01:31:46Z","timestamp":1684719106000},"page":"221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rtf1 Transcriptionally Regulates Neonatal and Adult Cardiomyocyte Biology"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3752-0208","authenticated-orcid":false,"given":"Adam D.","family":"Langenbacher","sequence":"first","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Crisman","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi Yi Stephanie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6730-7627","authenticated-orcid":false,"given":"Douglas J.","family":"Chapski","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Medicine, and Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Vondriska","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Medicine, and Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibin","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Medicine, and Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90025, USA"},{"name":"Signature Research Program in Cardiovascular and Metabolic Diseases, Duke-NUS School of Medicine and National Heart Center of Singapore, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7883-3270","authenticated-orcid":false,"given":"Chen","family":"Gao","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Medicine, and Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90025, USA"},{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8807-3607","authenticated-orcid":false,"given":"Jau-Nian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nrg3484","article-title":"Eukaryotic transcriptional dynamics: From single molecules to cell populations","volume":"14","author":"Coulon","year":"2013","journal-title":"Nat. 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