{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:24:58Z","timestamp":1789503898147,"version":"build-2803163510"},"reference-count":66,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:00:00Z","timestamp":1688947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL148733"],"award-info":[{"award-number":["HL148733"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["19TPA3480072"],"award-info":[{"award-number":["19TPA3480072"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001395","name":"Wisconsin Alumni Research Foundation","doi-asserted-by":"crossref","award":["AAH4884"],"award-info":[{"award-number":["AAH4884"]}],"id":[{"id":"10.13039\/100001395","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011089","name":"University of Wisconsin Foundation","doi-asserted-by":"crossref","award":["AAH5964"],"award-info":[{"award-number":["AAH5964"]}],"id":[{"id":"10.13039\/100011089","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,10]]},"abstract":"<jats:p>\n                    Human patients carrying genetic mutations in RNA binding motif 20 (RBM20) develop a clinically aggressive dilated cardiomyopathy (DCM). Genetic mutation knockin (KI) animal models imply that altered function of the arginine-serine-rich (RS) domain is crucial for severe DCM. To test this hypothesis, we generated an RS domain deletion mouse model (\n                    <jats:italic>Rbm20<\/jats:italic>\n                    <jats:sup>\u0394RS<\/jats:sup>\n                    ). We showed that\n                    <jats:italic>Rbm20<\/jats:italic>\n                    <jats:sup>\u0394RS<\/jats:sup>\n                    mice manifested DCM with mis-splicing of RBM20 target transcripts. We found that RBM20 was mis-localized to the sarcoplasm in\n                    <jats:italic>Rbm20<\/jats:italic>\n                    <jats:sup>\u0394RS<\/jats:sup>\n                    mouse hearts and formed RBM20 granules similar to those detected in mutation KI animals. In contrast, mice lacking the RNA recognition motif showed similar mis-splicing of major RBM20 target genes but did not develop DCM or exhibit RBM20 granule formation. Using in vitro studies with immunocytochemical staining, we demonstrated that only DCM-associated mutations in the RS domain facilitated RBM20 nucleocytoplasmic transport and promoted granule assembly. Further, we defined the core nuclear localization signal (NLS) within the RS domain of RBM20. Mutation analysis of phosphorylation sites in the RS domain suggested that this modification may be dispensable for RBM20 nucleocytoplasmic transport. Collectively, our findings revealed that disruption of RS domain\u2013mediated nuclear localization is crucial for severe DCM caused by NLS mutations.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.170001","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T12:00:32Z","timestamp":1684843232000},"source":"Crossref","is-referenced-by-count":20,"title":["Disruption of the nuclear localization signal in RBM20 is causative in dilated cardiomyopathy"],"prefix":"10.1172","volume":"8","author":[{"given":"Yanghai","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4013-4869","authenticated-orcid":true,"given":"Zachery R.","family":"Gregorich","sequence":"additional","affiliation":[{"name":"Department of Animal and Dairy Sciences, University of 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