Zhu Lijing, Yi Wei, Zhang Like, Qiu Chenyue, Sun Ning, He Jingwen, Feng Ping, Wu Qiong, Wang Guangyi, Wu Guosheng
Department of Burn Surgery, Changhai Hospital, Navy Medical University, Shanghai 200433, China.
Int J Mol Sci. 2025 May 28;26(11):5159. doi: 10.3390/ijms26115159.
Heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) is a multifunctional RNA-binding protein (RBP) that plays a central role in post-transcriptional regulation. Through its quasi-RNA recognition motifs and low-complexity domains, hnRNPH1 specifically binds guanine-rich RNA sequences, including G-quadruplex structures, to precisely modulate multiple aspects of RNA metabolism, such as alternative splicing, mRNA stability, translation, and subcellular localization. Accumulating evidence has implicated hnRNPH1 dysfunction in the pathogenesis of several human diseases. In cancer, hnRNPH1 often acts as a pro-tumorigenic factor, albeit in a context-dependent manner, influencing the alternative splicing of crucial oncogenes, mRNA stability, and tumor cell sensitivity to therapeutic agents. In the nervous system, hnRNPH1 is involved in neurodevelopment, neurodegenerative diseases, and drug addiction and plays an essential role in maintaining neuronal function and homeostasis. Furthermore, it exerts regulatory functions in reproductive system development and fertility and in non-neoplastic pathologies, including cardiovascular diseases, autoimmune disorders, and viral hepatitis. Given its pathophysiological significance, hnRNPH1 has emerged as a promising biomarker and therapeutic target. This review provides an overview of the structural basis and core molecular function of hnRNPH1. Its mechanisms of action and pathological significance in various diseases have also been detailed. Additionally, this review summarizes the current therapeutic strategies targeting hnRNPH1, discusses the associated challenges, outlines optimization approaches, and considers future research directions. Overall, this review aims to deepen our understanding of hnRNPH1 biology and inspire the development of novel diagnostic and therapeutic interventions.
不均一核核糖核蛋白H1（hnRNPH1）是一种多功能RNA结合蛋白（RBP），在转录后调控中发挥核心作用。通过其准RNA识别基序和低复杂性结构域，hnRNPH1特异性结合富含鸟嘌呤的RNA序列，包括G-四链体结构，以精确调节RNA代谢的多个方面，如可变剪接、mRNA稳定性、翻译和亚细胞定位。越来越多的证据表明hnRNPH1功能障碍与几种人类疾病的发病机制有关。在癌症中，hnRNPH1通常作为一种促肿瘤发生因子，尽管其作用具有背景依赖性，可影响关键癌基因的可变剪接、mRNA稳定性以及肿瘤细胞对治疗药物的敏感性。在神经系统中，hnRNPH1参与神经发育、神经退行性疾病和药物成瘾，并在维持神经元功能和体内平衡方面发挥重要作用。此外，它在生殖系统发育和生育以及非肿瘤性疾病（包括心血管疾病、自身免疫性疾病和病毒性肝炎）中发挥调节功能。鉴于其病理生理学意义，hnRNPH1已成为一个有前景的生物标志物和治疗靶点。本综述概述了hnRNPH1的结构基础和核心分子功能。还详细阐述了其在各种疾病中的作用机制和病理意义。此外，本综述总结了目前针对hnRNPH1的治疗策略，讨论了相关挑战，概述了优化方法，并考虑了未来的研究方向。总体而言，本综述旨在加深我们对hnRNPH1生物学的理解，并激发新型诊断和治疗干预措施的开发。
