The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Isabelle Draper, Wanting Huang, Suchita Pande, Aaron Zou, Timothy D. Calamaras, Richard H. Choe, Ana Correia-Branco, Ariel L. Mei, Howard H. Chen, Hannah R. Littel, Mekala Gunasekaran, Natalya M. Wells, Christine C. Bruels, Audrey L. Daugherty, Matthew J. Wolf, Peter B. Kang, Vicky K. Yang, Donna K. Slonim, Mary C. Wallingford, Robert M. Blanton
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Abstract

Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.

Abstract Image

剪接因子 hnRNPL 在不同物种中对心肌的调控是一致的,并在心力衰竭中发生改变。
心力衰竭(HF)发病率很高。人们对心力衰竭的发病机制仍不完全清楚。剪接因子(SF)可控制前核糖核酸(pre-mRNA)的替代剪接,调节心脏结构和功能。本研究调查了剪接因子异质核糖核蛋白-L(hnRNPL)在衰竭心脏中的调控。经主动脉缩窄诱发高房颤的小鼠和高房颤患者的左心室组织中,hnRNPL 蛋白增加。在左心室组织中,hnRNPL主要在细胞核中被检测到。在果蝇中敲除 hnRNPL 同源物 Smooth 会诱发心肌病。对预测的小鼠和人类 hnRNPL 结合位点的计算分析表明,hnRNPL 介导了肌球蛋白的替代剪接,这在 C2C12 肌母细胞中得到了证实。这些发现确定了 hnRNPL 是心脏功能障碍的传感器,并表明 hnRNPL 的紊乱会影响高频心肌病的替代剪接。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
7.00
自引率
2.90%
发文量
303
审稿时长
1.0 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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