{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T11:00:39Z","timestamp":1770462039493,"version":"3.49.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,7,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Although the roles of alpha\u2010myosin heavy chain (\u03b1\u2010MyHC) and beta\u2010myosin heavy chain (\u03b2\u2010MyHC) proteins in cardiac contractility have long been appreciated, the biological contribution of another closely related sarcomeric myosin family member, MYH7b (myosin heavy chain 7b), has become a matter of debate. In mammals, MYH7b mRNA is transcribed but undergoes non\u2010productive alternative splicing that prevents protein expression in a tissue\u2010specific manner, including in the heart. However, several studies have recently linked MYH7b variants to different cardiomyopathies or have reported MYH7b protein expression in mammalian hearts.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">By analyzing mammalian cardiac transcriptome and proteome data, we show that the vast majority of MYH7b RNA is subject to exon skipping and cannot be translated into a functional myosin molecule. Notably, we discovered a lag in the removal of introns flanking the alternatively spliced exon, which could retain the non\u2010coding RNA in the nucleus. This process could play a significant role in controlling MYH7b expression as well as the activity of other cardiac genes. Consistent with the negligible level of full\u2010length protein coding mRNA, no MYH7b protein expression was detected in adult mouse, rat, and human hearts by Western blot analysis. Furthermore, proteome surveys including quantitative mass spectrometry analyses revealed only traces of cardiac MYH7b protein and even then, only in a subset of individual samples.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The comprehensive analysis presented here suggests that previous studies showing cardiac MYH7b protein expression were likely attributable to antibody cross\u2010reactivity. More importantly, our data predict that the MYH7b disease\u2010associated variants may operate through the alternately spliced RNA itself.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.020965","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T09:56:11Z","timestamp":1625565371000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Nonproductive Splicing Prevents Expression of MYH7b Protein in the Mammalian Heart"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7082-5484","authenticated-orcid":false,"given":"Lindsey A.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology University of Colorado Boulder Boulder CO"},{"name":"BioFrontiers InstituteUniversity of Colorado Boulder Boulder CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7559-3977","authenticated-orcid":false,"given":"Lindsey J.","family":"Broadwell","sequence":"additional","affiliation":[{"name":"BioFrontiers InstituteUniversity of Colorado Boulder Boulder CO"},{"name":"Department of Biochemistry University of Colorado Boulder Boulder CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8817-1511","authenticated-orcid":false,"given":"Massimo","family":"Buvoli","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology University of Colorado Boulder Boulder CO"},{"name":"BioFrontiers InstituteUniversity of Colorado Boulder Boulder CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-4810","authenticated-orcid":false,"given":"Leslie A.","family":"Leinwand","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology University of Colorado Boulder Boulder CO"},{"name":"BioFrontiers InstituteUniversity of Colorado Boulder Boulder CO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/cm.21089"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-91"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-019-1627-y"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a004093"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.181008"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01370-09"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.013318"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.6A7084.2006"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.10.013"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2797-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.010378"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.04.021"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13302"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01747-2"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA119.001878"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr5007685"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0046-2"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.010"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1120"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_3_2_22_2","first-page":"387","article-title":"Distributions of exons and introns in the human genome","volume":"4","author":"Sakharkar MK","year":"2004","unstructured":"Sakharkar MK, Chow VTK, Kangueane P. 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