hnRNP A1 in RNA metabolism regulation and as a potential therapeutic target

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.

Automated summary

This article highlights the importance of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) in regulating RNA metabolism and its dysregulation in various diseases. The selective binding sites of hnRNP A1 to RNA and DNA are summarized, along with the co-regulatory factors that interact with hnRNP A1. The potential therapeutic implications of targeting hnRNP A1 are discussed, including small-molecule drugs and biomedicines.