Evidence map›Paper›PMID 41214391›Full record

ArticleEMBO molecular medicine2025

RBMS1 orchestrates cardiac hypertrophy by facilitating CTTN splice-switching and sarcomere dynamics.

Liangliang Li, Tianyu Li, Bin Wang, Jiayue Feng, Nan Zhang, Jing Zhang, Zhihui Niu, Wei Li, Huiying Gao, Qianqian Wang and 10 more

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Article in EMBO molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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20 authors.

Liangliang Li *State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.ORCID http://orcid.org/0009-0008-5493-4809
Tianyu Li *State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Bin Wang *Department of Cardiovascular Ultrasound, Zhongnan Hospital of Wuhan University, Wuhan, China.
Jiayue Feng *State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Nan ZhangDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Jing ZhangState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Zhihui NiuState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.ORCID http://orcid.org/0000-0003-1945-7687
Wei LiState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Huiying GaoState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Qianqian WangState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Yang LiuState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Yi ChenState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Yixin ZhangState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Yu BianState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Tengfei PanState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Siqi ShengThe Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Xuelian LiState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Jinping LiuDepartment of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China. liujinping@znhospital.cn.ORCID http://orcid.org/0000-0002-9384-4880
Baofeng YangState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China. yangbf@ems.hrbmu.edu.cn.ORCID http://orcid.org/0000-0002-0125-1608
Haihai LiangState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China. lianghaihai@ems.hrbmu.edu.cn.ORCID http://orcid.org/0000-0003-4446-7035

Funding

MOST | National Natural Science Foundation of China (NSFC) 32171127MOST | National Natural Science Foundation of China (NSFC) 82330011MOST | National Natural Science Foundation of China (NSFC) 82470413MOST | National Natural Science Foundation of China (NSFC) U24A20645| Postdoctoral Research Foundation of China (China Postdoctoral Research Foundation) 2024MD753941The CAMS Innovation Fund for Medical Sciences CIFMS, 2020-I2M-5-003The Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0537900The Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0537908
6 · The paper itself

Abstract

Cardiac hypertrophy is one of the significant causes of heart failure and is closely related to the rising rate of hospitalization and readmissions. Given the diverse regulatory roles of alternative splicing in cardiovascular diseases, RNA-binding proteins have attracted increasing research attention. Here, for the first time, we discovered elevated expression of RBMS1 in heart tissues of patients with dilated cardiomyopathy and in mice with cardiac hypertrophy. We demonstrated that RBMS1 activated the PI3K/AKT signaling pathway by promoting the splicing CTTN to generate CTTN-Δe11 splicing isoform, resulting in cytoskeleton and sarcomere damage in cardiomyocytes. Additionally, pharmacological inhibition of RBMS1 by nortriptyline alleviated cardiac hypertrophy and heart failure. These results provide a new perspective for developing novel therapeutic approaches for cardiac hypertrophy and establish a theoretical basis for targeting RBMS1 in the clinical treatment of cardiac hypertrophy.

Indexed as

Alternative SplicingCardiomegalyRNA-Binding ProteinsSarcomeresAnimalsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLMyocytes, CardiacPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA-Binding ProteinsAlternative SplicingCardiac HypertrophyCTTNRBMS1Sarcomere

Identifiers

PMID41214391
PMCPMC12686484

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