Isabelle Draper, Wanting Huang, Suchita Pande, Aaron Zou, Timothy D Calamaras, Richard H Choe, Ana Correia-Branco, Ariel L Mei, Howard H Chen, Hannah R Littel, Mekala Gunasekaran, Natalya M Wells, Christine C Bruels, Audrey L Daugherty, Matthew J Wolf, Peter B Kang, Vicky K Yang, Donna K Slonim, Mary C Wallingford, Robert M Blanton
{"title":"剪接因子 hnRNPL 在不同物种中对心肌的调控是一致的,并在心力衰竭中发生改变。","authors":"Isabelle Draper, Wanting Huang, Suchita Pande, Aaron Zou, Timothy D Calamaras, Richard H Choe, Ana Correia-Branco, Ariel L Mei, Howard H Chen, Hannah R Littel, Mekala Gunasekaran, Natalya M Wells, Christine C Bruels, Audrey L Daugherty, Matthew J Wolf, Peter B Kang, Vicky K Yang, Donna K Slonim, Mary C Wallingford, Robert M Blanton","doi":"10.1002/1873-3468.15020","DOIUrl":null,"url":null,"abstract":"<p><p>Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure.\",\"authors\":\"Isabelle Draper, Wanting Huang, Suchita Pande, Aaron Zou, Timothy D Calamaras, Richard H Choe, Ana Correia-Branco, Ariel L Mei, Howard H Chen, Hannah R Littel, Mekala Gunasekaran, Natalya M Wells, Christine C Bruels, Audrey L Daugherty, Matthew J Wolf, Peter B Kang, Vicky K Yang, Donna K Slonim, Mary C Wallingford, Robert M Blanton\",\"doi\":\"10.1002/1873-3468.15020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.</p>\",\"PeriodicalId\":12142,\"journal\":{\"name\":\"FEBS Letters\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"FEBS Letters\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/1873-3468.15020\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/1873-3468.15020","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure.
Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.
期刊介绍:
FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.