dsRBPs

Double-stranded RNA-binding proteins (dsRBPs) are a diverse group of proteins that recognize and bind double-stranded RNA (dsRNA) through one or more double-stranded RNA-binding domains. They play central roles in RNA processing, editing, transport, translation regulation, and antiviral responses across eukaryotes.

Most dsRBPs contain one or more dsRNA-binding domains (dsRBDs), typically about 65–70 amino acids long, that mediate sequence-independent recognition of dsRNA by contacts in the minor groove. The dsRBD fold is distinct from catalytic RNase domains, and proteins may also carry additional regulatory or catalytic modules that enable a variety of functions.

In RNA silencing and processing, dsRBPs often act as cofactors for Dicer and Argonaute complexes. In humans, TAR RNA-binding protein (TRBP) and PACT associate with Dicer to aid siRNA and miRNA maturation and loading into RISC, while in Drosophila the R2D2 protein partners with Dicer-2 to transfer siRNA to the effector complex. In RNA editing, ADAR1 and ADAR2 bind dsRNA substrates and catalyze adenosine-to-inosine deamination, influencing transcript diversity. In innate immunity, the dsRNA-binding protein PKR detects viral dsRNA and triggers translational shutdown, and Staufen proteins mediate mRNA localization and regulation, including decay pathways in some contexts.

Representative examples include human ADAR1, ADAR2, and ADAR3 (the latter being catalytically inactive), Staufen1 and Staufen2, TRBP, and PACT; and Drosophila R2D2. dsRBPs are conserved across eukaryotes and contribute to post-transcriptional gene regulation, RNA metabolism, and genome defense.