hnRNP A1 in RNA metabolism regulation and as a potential therapeutic target.
hnRNP A1 in RNA metabolism regulation and as a potential therapeutic target.
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hnRNP A1 在 RNA 代谢调节中的作用及其作为潜在治疗靶点
DOI：
10.3389/fphar.2022.986409
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
受各种RNA结合蛋白调节的RNA代谢异常，可对多种疾病产生功能性后果。异质性核糖核蛋白A1(HnRNP A1)是一种重要的RNA结合蛋白，调节着多种RNA代谢过程，包括转录、Pre-mRNA的选择性剪接、翻译、miRNA加工和mRNA的稳定性。作为一种有效的剪接因子，hnRNP A1可以通过与外显子或内含子上的剪接位点和调控元件结合，调节包括自身在内的多种剪接事件，与其他合作或拮抗剪接因子合作。HnRNP A1可以通过直接与启动子相互作用或间接影响Pol II活性来调节基因转录。此外，通过与mRNAs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的翻译。HnRNP A1可以通过与3‘-UTR、miRNAs的生物发生和无义介导的mRNA衰退(NMD)途径的特定位置结合来改变mRNAs的稳定性。在这篇综述中，我们总结了hnRNP A1与RNA和DNA结合的选择性位点，以及与hnRNP A1相互作用的协同调节因子。鉴于hnRNP A1在各种疾病中的调节失调，特别是在癌症和神经退行性疾病中，以hnRNP A1为靶点进行治疗是非常有希望的。因此，本综述还提供了针对hnRNP A1的小分子药物、生物医学和新的治疗策略。
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.
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影响因子：
29
作者：
Babic I;Anderson ES;Tanaka K;Guo D;Masui K;Li B;Zhu S;Gu Y;Villa GR;Akhavan D;Nathanson D;Gini B;Mareninov S;Li R;Camacho CE;Kurdistani SK;Eskin A;Nelson SF;Yong WH;Cavenee WK;Cloughesy TF;Christofk HR;Black DL;Mischel PS
通讯作者：
Mischel PS
影响因子：
7.3
作者：
Busch, Anke;Hertel, Klemens J.
通讯作者：
Hertel, Klemens J.
影响因子：
5.4
作者：
Bruun GH;Doktor TK;Borch-Jensen J;Masuda A;Krainer AR;Ohno K;Andresen BS
通讯作者：
Andresen BS
影响因子：
4.5
作者：
Cienikova, Zuzana;Jayne, Sandrine;Maris, Christophe
通讯作者：
Maris, Christophe
影响因子：
9.8
作者：
An P;Grabowski PJ
通讯作者：
Grabowski PJ