{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T19:29:48Z","timestamp":1784575788258,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011279","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000}}],"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Arizona Undergraduate Biology Research Program"},{"name":"\u201cBilly\u201d Gieszl and Walter and Vinnie Hinz Pediatric\/Congenital Heart Disease Awards from UArizona Sarver Heart Center"},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL123078"],"award-info":[{"award-number":["R01HL123078"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Czarina M. & Humberto S. Lopez Endowed Chair for Excellence in Cardiovascular Research"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>The leiomodin (Lmod) family of actin-binding proteins play a critical role in muscle function, highlighted by the fact that mutations in all three family members (LMOD1-3) result in human myopathies. Mutations in the cardiac predominant isoform, LMOD2 lead to severe neonatal dilated cardiomyopathy. Most of the disease-causing mutations in the LMOD gene family are nonsense, or frameshift, mutations predicted to result in expression of truncated proteins. However, in nearly all cases of disease, little to no LMOD protein is expressed. We show here that nonsense-mediated mRNA decay, a cellular mechanism which eliminates mRNAs with premature termination codons, underlies loss of mutant protein from two independent LMOD2 disease-causing mutations. Furthermore, we generated steric-blocking oligonucleotides that obstruct deposition of the exon junction complex, preventing nonsense-mediated mRNA decay of mutant LMOD2 transcripts, thereby restoring mutant protein expression. Our investigation lays the initial groundwork for potential therapeutic intervention in LMOD-linked myopathies.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011279","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T17:49:17Z","timestamp":1715795357000},"page":"e1011279","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Human disease-causing mutations result in loss of leiomodin 2 through nonsense-mediated mRNA decay"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7475-6949","authenticated-orcid":true,"given":"Christopher T.","family":"Pappas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Mayfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3952-2903","authenticated-orcid":true,"given":"Ava E.","family":"Dickerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8595-0552","authenticated-orcid":true,"given":"Lei","family":"Mi-Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0044-2074","authenticated-orcid":true,"given":"Carol C.","family":"Gregorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"issue":"13","key":"pgen.1011279.ref001","doi-asserted-by":"crossref","first-page":"E2739","DOI":"10.1073\/pnas.1620507114","article-title":"Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice","volume":"114","author":"D Halim","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pgen.1011279.ref002","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1172\/JCI75199","article-title":"Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy","volume":"124","author":"M Yuen","year":"2014","journal-title":"J Clin Invest"},{"issue":"7","key":"pgen.1011279.ref003","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/jum.14520","article-title":"LMOD3-Associated Nemaline Myopathy: Prenatal Ultrasonographic, Pathologic, and Molecular Findings","volume":"37","author":"M Berkenstadt","year":"2018","journal-title":"J Ultrasound Med"},{"issue":"2","key":"pgen.1011279.ref004","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.nmd.2018.12.009","article-title":"Long-term follow-up and characteristic pathological findings in severe nemaline myopathy due to LMOD3 mutations","volume":"29","author":"E Michael","year":"2019","journal-title":"Neuromuscul Disord"},{"issue":"18","key":"pgen.1011279.ref005","doi-asserted-by":"crossref","first-page":"e1690","DOI":"10.1212\/WNL.0000000000006428","article-title":"Evidence of mild founder LMOD3 mutations causing nemaline myopathy 10 in Germany and Austria","volume":"91","author":"UA Schatz","year":"2018","journal-title":"Neurology"},{"issue":"47","key":"pgen.1011279.ref006","doi-asserted-by":"crossref","first-page":"e2315820120","DOI":"10.1073\/pnas.2315820120","article-title":"Jr., Mayfield RM, Larrinaga TM, Kostyukova AS, Gregorio CC. 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