TAR RNA-binding protein 2 (TRBP) (TRBP)

TAR RNA-binding protein 2 (TRBP) is a double-stranded RNA-binding protein that serves as a critical regulator of the RNA interference (RNAi) pathway and the cellular response to viral infection. It is a key component of the RISC-loading complex, where it partners with Dicer and Argonaute 2 to facilitate the processing of precursor microRNAs into mature miRNAs. Originally identified for its ability to bind the HIV-1 trans-activation response (TAR) RNA element, TRBP enhances viral gene expression and replication while simultaneously inhibiting the interferon-induced protein kinase R (PKR), a sensor that normally restricts translation during stress or infection. In various human pathologies, particularly cancer, TRBP is frequently overexpressed or mutated, leading to deregulated miRNA biogenesis and the suppression of innate immune defenses. As a result, TRBP is an attractive therapeutic target for antiviral and anticancer drug development, with research focusing on small molecules like enoxacin that can modulate its activity in miRNA processing. Experimental approaches using siRNAs to knock down TRBP have also demonstrated efficacy in inhibiting HIV-1 production. Overall, TRBP serves as a multifunctional hub connecting RNA processing, innate immunity, and viral pathogenesis.

Other names

TARBP2TRBP1TRBP2RISC-loading complex RNA-binding subunitTrans-activation response RNA-binding protein 2

Enoxacin acts as a small molecule enhancer of microRNA biogenesis by binding to the TRBP-Dicer complex to facilitate miRNA processing. Experimental siRNAs target TRBP mRNA for degradation to inhibit its role in viral replication and PKR suppression.