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可变剪接分析揭示肾上腺素能信号传导是心脏中蛋白质精氨酸甲基转移酶5(PRMT5)的新靶点。

Alternative Splicing Analysis Reveals Adrenergic Signaling as a Novel Target for Protein Arginine Methyltransferase 5 (PRMT5) in the Heart.

作者信息

Jiao Shouye, Zhang Yimeng, Yang Xiao, Wang Jian, Li Zhenhua

机构信息

Department of Cell Biology, School of Basic Medicine, Qingdao University, Qingdao 266071, China.

State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China.

出版信息

Int J Mol Sci. 2025 Mar 5;26(5):2301. doi: 10.3390/ijms26052301.

DOI:10.3390/ijms26052301
PMID:40076920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11899901/
Abstract

Adrenergic signaling is critical for maintaining cardiac function and works by regulating heart rate, contractility, and stress responses. Protein arginine methyltransferase 5 (PRMT5), a key enzyme involved in gene expression, signal transduction, and RNA processing, has been revealed to be an important factor in heart disease. However, its specific effects on adrenergic signaling have not been fully elucidated. In this study, we examined the role of PRMT5 in the heart by analyzing alternative splicing events in cardiac tissues from -deficient mice. High-throughput RNA sequencing and bioinformatics analyses identified significant alterations in alternative splicing, particularly in genes related to adrenergic signaling, which were further validated using reverse transcription PCR. These results underscore the role of PRMT5 as an important regulator of alternative splicing in the heart and identify adrenergic signaling as a novel target. Collectively, our findings offer new insights into the molecular mechanisms underlying cardiac function and suggest that PRMT5 is a potential therapeutic target for heart diseases.

摘要

肾上腺素能信号传导对于维持心脏功能至关重要,其通过调节心率、收缩力和应激反应发挥作用。蛋白质精氨酸甲基转移酶5(PRMT5)是一种参与基因表达、信号转导和RNA加工的关键酶,已被证明是心脏病的一个重要因素。然而,其对肾上腺素能信号传导的具体影响尚未完全阐明。在本研究中,我们通过分析PRMT5基因缺陷小鼠心脏组织中的可变剪接事件,研究了PRMT5在心脏中的作用。高通量RNA测序和生物信息学分析确定了可变剪接的显著变化,特别是与肾上腺素能信号传导相关的基因,这通过逆转录PCR进一步得到验证。这些结果强调了PRMT5作为心脏中可变剪接重要调节因子的作用,并将肾上腺素能信号传导确定为一个新的靶点。总体而言,我们的研究结果为心脏功能的分子机制提供了新的见解,并表明PRMT5是心脏病的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27bb/11899901/c609bfb85eb0/ijms-26-02301-g006.jpg
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本文引用的文献

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J Biol Chem. 2025 Mar;301(3):108201. doi: 10.1016/j.jbc.2025.108201. Epub 2025 Jan 16.
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Alternative Splicing in the Heart: The Therapeutic Potential of Regulating the Regulators.心脏中的可变剪接:调控调控因子的治疗潜力
Int J Mol Sci. 2024 Dec 4;25(23):13023. doi: 10.3390/ijms252313023.
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The alternative splicing landscape of infarcted mouse heart identifies isoform level therapeutic targets.梗死小鼠心脏的可变剪接图谱确定了异构体水平的治疗靶点。
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Transcript splicing optimizes the thymic self-antigen repertoire to suppress autoimmunity.转录剪接优化了胸腺自身抗原库,以抑制自身免疫。
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PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.PRMT5 介导的同源重组修复对于维持神经祖细胞的基因组完整性至关重要。
Cell Mol Life Sci. 2024 Mar 8;81(1):123. doi: 10.1007/s00018-024-05154-x.
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Alpha-synuclein promotes PRMT5-mediated H4R3me2s histone methylation by interacting with the BAF complex.α-突触核蛋白通过与 BAF 复合物相互作用,促进 PRMT5 介导的 H4R3me2s 组蛋白甲基化。
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