Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells

作     者：Peter Zorn Jaime Calvo Sánchez Tala Alakhras Barbara Schreier Michael Gekle Stefan Hüttelmaier Marcel Köhn 

作者机构：Junior Group‘Non-coding RNAs and RBPs in Human Diseases’Medical FacultyUniversity of Halle–Wittenberg06120 Halle(Saale)Germany Julius Bernstein Institute of PhysiologyMedical FacultyUniversity of Halle–Wittenberg06112 Halle(Saale)Germany Institute of Molecular MedicineMedical FacultyUniversity of Halle–Wittenberg06120 Halle(Saale)Germany 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2024年第16卷第1期

页      面：54-65页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by grants from the Deutsche Forschungsgemeinschaft[DFG,German Research Foundation RTG 2467,project number 391498659‘Intrinsically disordered proteins—molecular principles,cellular functions,and diseases’ FOR 5433,project number 468534282‘RNA in focus(RIF):from mechanisms to novel therapeutic strategies in cancer treatment’] the Wilhelm-Roux-Program(Medical Faculty,Martin-Luther-University Halle–Wittenberg) 

主　　题：Rbfox1 alternative splicing focal adhesion cardiac muscle cells 

摘      要：Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein ***,it remains challenging to identify physiologically relevant and tissue-selective proteins that are generated by alternative ***,we investigated the target spectrum of the splicing factor Rbfox1 in the cardiac muscle context in more *** using a combination of in silico target prediction and in-cell validation,we identified several focal adhesion proteins as alternative splicing targets of *** focused on the alternative splicing patterns of vinculin(metavinculin isoform)and paxillin(extended paxillin isoform)and identified both as potential Rbfox1 *** analyses suggested that both isoforms are promoted by Rbfox1 due to binding in the *** adhesions play an important role in the cardiac muscle context,since they mainly influence cell shape,cytoskeletal organization,and cell–matrix *** data confirmed that depletion of Rbfox1 changed cardiomyoblast morphology,cytoskeletal organization,and multinuclearity after differentiation,which might be due to changes in alternative splicing of focal adhesion ***,our results indicate that Rbfox1 promotes alternative splicing of focal adhesion genes in cardiac muscle cells,which might contribute to heart disease progression,where downregulation of Rbfox1 is frequently observed.