RBM15 Protects From Myocardial Infarction by Stabilizing NAE1

IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Hao Cheng MD, PhD , Jian Wu MD, PhD , Linnan Li MD, PhD , Xiaoyue Song MD, PhD , Junqiang Xue MD, PhD , Yuekai Shi MD, PhD , Yunzeng Zou MD, PhD , Jianying Ma MD, PhD , Junbo Ge MD, PhD
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引用次数: 0

Abstract

RNA-binding proteins play multiple roles in several biological processes. However, the roles of RBM15—an important RNA-binding protein and a significant regulator of RNA methylation—in cardiovascular diseases remain elusive. This study aimed to investigate the biological function of RBM15 and its fundamental mechanisms in myocardial infarction (MI). Methylated RNA immunoprecipitation sequencing was used to explore the N6-methyladenosine (m6A) difference between MI and normal tissues. Our findings showed the elevated level of m6A in MI, and its transcription profile in both MI and normal tissues. RBM15 was the main regulator and its overexpression attenuated apoptosis in cardiomyocytes and improved cardiac function in mice after MI. Then, we used one target NEDD8 activating enzyme E1 subunit and its inhibitor (MLN4924) to investigate the impact of RBM15 targets on cardiomyocytes. Finally, the enhanced m6A methylation in the presence of RBM15 overexpression led to the increased expression and stability of NEDD8 activating enzyme E1 subunit. Our findings suggest that the enhanced m6A level is a protective mechanism in MI, and RBM15 is significantly upregulated in MI and promotes cardiac function. This study showed that RBM15 affected MI by stabilizing its target on the cell apoptosis function, which might provide a new insight into MI therapy.

Abstract Image

RBM15 通过稳定 NAE1 防止心肌梗死
RNA 结合蛋白在多个生物过程中发挥着多重作用。然而,RBM15--一种重要的 RNA 结合蛋白和 RNA 甲基化的重要调控因子--在心血管疾病中的作用仍不明确。本研究旨在探讨 RBM15 在心肌梗死(MI)中的生物学功能及其基本机制。研究采用甲基化 RNA 免疫沉淀测序技术,探讨了心肌梗死与正常组织中 N6-甲基腺苷(m6A)的差异。我们的研究结果表明,在心肌梗死中,m6A的水平升高,其在心肌梗死和正常组织中的转录情况也是如此。RBM15是主要的调控因子,其过表达可减轻心肌细胞的凋亡,并改善心肌梗死后小鼠的心脏功能。然后,我们利用一个靶点 NEDD8 激活酶 E1 亚基及其抑制剂(MLN4924)来研究 RBM15 靶点对心肌细胞的影响。最后,在 RBM15 过表达的情况下,m6A 甲基化增强导致 NEDD8 激活酶 E1 亚基的表达和稳定性增加。我们的研究结果表明,m6A水平的增强是心肌缺血的一种保护机制,而RBM15在心肌缺血中显著上调并促进心脏功能。本研究表明,RBM15通过稳定细胞凋亡功能靶点来影响心肌梗死,这可能为心肌梗死的治疗提供了新的思路。
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来源期刊
JACC: Basic to Translational Science
JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
14.20
自引率
1.00%
发文量
161
审稿时长
16 weeks
期刊介绍: JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.
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