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

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.

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Publication Details

Journal
EMBO Molecular Medicine
Published
2025-11-10
DOI
https://doi.org/10.1038/s44321-025-00334-z
Citations
1
Primary Topic
RNA Research and Splicing
Type
article
Field-Weighted Citation Impact
0.81
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article

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

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EMBO Molecular Medicine
RNA Research and Splicing
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article

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

Siqi Sheng, Yi Chen, Haihai Liang, Huiying Gao, Zhihui Niu, Jinping Liu, Tengfei Pan, Xuelian Li, Wei Li, Jing Zhang, Yixin Zhang, Yang Liu, Tianyu Li, Qianqian Wang, Baofeng Yang, Yu Bian, Nan Zhang, Jiayue Feng, Bin Wang, Liangliang Li
article en
1 citations

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.

EMBO Molecular MedicineVol. 17(12)
Harbin Engineering University (CN), Harbin Medical University (CN), Hohai University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Wuhan University (CN), Ministry of Education (KR), Zhongnan Hospital of Wuhan University (CN), Second Affiliated Hospital of Harbin Medical University (CN), First Affiliated Hospital of Harbin Medical University (CN)
Openalex Percentile: Top 22%
RNA Research and Splicing
0.81
DOIOpen Access PDFOpenAlex
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