A-form double-stranded RNA (A-form dsRNA)

A-form double-stranded RNA (dsRNA) is the primary structural conformation of duplex RNA, characterized by a deep, narrow major groove and a shallow, wide minor groove [12, 16]. It serves as a critical Pathogen-Associated Molecular Pattern (PAMP) that signals the presence of viral infection to the host's innate immune system [5, 9]. Recognition of A-form dsRNA by pattern recognition receptors (PRRs) such as Toll-like receptor 3 (TLR3), RIG-I, and MDA5 triggers the production of Type I interferons and pro-inflammatory cytokines to establish an antiviral state [3, 5, 9]. Beyond its role in immunity, the A-form geometry is essential for the mechanism of RNA interference (RNAi), where small interfering RNAs (siRNAs) adopt this conformation to be recognized by the RNA-induced silencing complex (RISC) for targeted gene silencing [8, 18]. Therapeutically, synthetic dsRNA analogues like poly I:C and rintatolimod are utilized as immunomodulators and vaccine adjuvants to enhance anti-tumor and anti-viral responses [3, 5]. However, the clinical application of dsRNA is challenged by significant safety concerns, including the potential for inducing systemic "cytokine storms" and off-target effects [3, 10, 17].

Other names

dsRNADouble-stranded RNAA-RNARNA duplexDuplex RNA

Agonism of pattern recognition receptors (PRRs) such as TLR3, RIG-I, and MDA5 to induce Type I interferons and pro-inflammatory cytokines; serving as a substrate for the RNA-induced silencing complex (RISC) to mediate sequence-specific mRNA degradation.