Feng Jianguo, Zhou Jianlong, Lin Yunxiao, Huang Wenhua
Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Affiliated Xinhui Hospital, People's Hospital of Xinhui District, Southern Medical University, Jiangmen, Guangdong Province, China.
Front Pharmacol. 2022 Oct 21;13:986409. doi: 10.3389/fphar.2022.986409. eCollection 2022.
Abnormal RNA metabolism, regulated by various RNA binding proteins, can have functional consequences for multiple diseases. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an important RNA binding protein, that regulates various RNA metabolic processes, including transcription, alternative splicing of pre-mRNA, translation, miRNA processing and mRNA stability. As a potent splicing factor, hnRNP A1 can regulate multiple splicing events, including itself, collaborating with other cooperative or antagonistical splicing factors by binding to splicing sites and regulatory elements in exons or introns. hnRNP A1 can modulate gene transcription by directly interacting with promoters or indirectly impacting Pol II activities. Moreover, by interacting with the internal ribosome entry site (IRES) or 3'-UTR of mRNAs, hnRNP A1 can affect mRNA translation. hnRNP A1 can alter the stability of mRNAs by binding to specific locations of 3'-UTR, miRNAs biogenesis and Nonsense-mediated mRNA decay (NMD) pathway. In this review, we conclude the selective sites where hnRNP A1 binds to RNA and DNA, and the co-regulatory factors that interact with hnRNP A1. Given the dysregulation of hnRNP A1 in diverse diseases, especially in cancers and neurodegeneration diseases, targeting hnRNP A1 for therapeutic treatment is extremely promising. Therefore, this review also provides the small-molecule drugs, biomedicines and novel strategies targeting hnRNP A1 for therapeutic purposes.
由多种RNA结合蛋白调控的异常RNA代谢，会对多种疾病产生功能性影响。异质性细胞核核糖核蛋白A1（hnRNP A1）是一种重要的RNA结合蛋白，它调控多种RNA代谢过程，包括转录、前体mRNA的可变剪接、翻译、miRNA加工以及mRNA稳定性。作为一种有效的剪接因子，hnRNP A1可以调控多种剪接事件，包括其自身的剪接，它通过与外显子或内含子中的剪接位点和调控元件结合，与其他协同或拮抗的剪接因子协同作用。hnRNP A1可以通过直接与启动子相互作用或间接影响RNA聚合酶II的活性来调节基因转录。此外，通过与mRNA的内部核糖体进入位点（IRES）或3'-UTR相互作用，hnRNP A1可以影响mRNA翻译。hnRNP A1可以通过与3'-UTR的特定位置、miRNA生物合成和无义介导的mRNA降解（NMD）途径结合来改变mRNA的稳定性。在本综述中，我们总结了hnRNP A与RNA和DNA结合的选择性位点，以及与hnRNP A相互作用的共调节因子。鉴于hnRNP A在多种疾病中失调，尤其是在癌症和神经退行性疾病中，将hnRNP A作为治疗靶点极具前景。因此，本综述还提供了针对hnRNP A用于治疗目的的小分子药物、生物药物和新策略。
