RNA-binding profiles of CKAP4 in human myocardial tissues. RNA-binding profiles of CKAP4 in human myocardial tissues

CKAP4 as one of cardiac activated-myofibroblast protein markers may be involved in cardiac fibrosis. We assumed that CKAP4 hold a role in the regulation of cardiac fibrotic remodeling as an RNA-binding protein. Using improved RNA immunoprecipitation and sequencing (iRIP-seq), we sought to analyze the RNAs bound by CKAP4 in normal atrial muscle (IP1 group) and remodeling fibrotic atrial muscle (IP2 group) from patients with cardiac valvular disease.Binding peak-related gene cluster enrichment analysis showed these genes were mainly involved in biological processes such as signal transduction, protein phosphorylation, axonal guidance, and cell connection. Through gene annotation and correlation analysis of binding-peaks reads, we found that at least four lncRNAs including LINC00504, FLJ22447, RP11-326N17.2 and HELLPAR were CKAP4 potential binding lncRNAs in myocardial tissues.We reveal certain RNA-binding features of CKAP4 suggesting a relevant role as an unconventional RNA-binding protein in cardiac remodeling process. Overall design: iRIP-seqencing in normal atrial muscle (IP1 group) and remodeling fibrotic atrial muscle (IP2 group) from patients with cardiac valvular disease.

细胞骨架相关蛋白4（CKAP4）作为心脏活化肌成纤维细胞蛋白标志物之一，可能参与心脏纤维化进程。我们假设CKAP4作为RNA结合蛋白，在心脏纤维化重构的调控中发挥作用。本研究采用改进型RNA免疫共沉淀测序（iRIP-seq）技术，分析心脏瓣膜病患者正常心房肌组织（IP1组）与纤维化重构心房肌组织（IP2组）中CKAP4结合的RNA分子。结合峰相关基因簇富集分析结果显示，这些基因主要参与信号转导、蛋白质磷酸化、轴突导向以及细胞连接等生物学过程。通过对结合峰读段进行基因注释与相关性分析，我们发现心肌组织中至少存在4种长链非编码RNA（lncRNA），包括LINC00504、FLJ22447、RP11-326N17.2及HELLPAR，均为CKAP4的潜在结合lncRNA。本研究揭示了CKAP4的部分RNA结合特性，表明其作为非常规RNA结合蛋白在心脏重构过程中发挥相关作用。整体实验设计：对心脏瓣膜病患者的正常心房肌组织（IP1组）与纤维化重构心房肌组织（IP2组）开展iRIP-seq测序分析。