DsRNA

Double-stranded RNA (dsRNA) refers to RNA molecules in which two complementary strands form a duplex, resembling a short segment of RNA that has folded back on itself. In cells, dsRNA is unusual for endogenous transcripts but common as replication intermediates of many RNA viruses and as a product of RNA interference pathways. The length and sequence of dsRNA can vary widely, from tens to thousands of base pairs, with base pairing and helical geometry typical of RNA.

Biology and sensing of dsRNA are closely tied to antiviral defense and gene regulation. In many organisms, long dsRNA triggers RNA interference (RNAi), a gene-silencing mechanism. In this pathway, the enzyme Dicer processes long dsRNA into small interfering RNAs (siRNAs) that are loaded into the RNA-induced silencing complex (RISC). The guide strand directs RISC to complementary messenger RNA, leading to cleavage and degradation and thereby silencing the gene. dsRNA can also originate from bidirectional transcription or structured noncoding RNAs and contribute to endogenous regulatory networks.

In metazoans, dsRNA is a key trigger of innate immune responses. In mammals, recognition involves sensors such as MDA5 and RIG-I, which detect dsRNA and initiate interferon signaling, while PKR binds dsRNA to inhibit translation, and the 2'-5' oligoadenylate synthetase–RNase L pathway can degrade RNA. Plants and invertebrates rely more heavily on RNAi-based antiviral defenses, though they also employ dsRNA-sensing pathways.

dsRNA is a widely used research tool for gene knockdown through RNAi and has potential therapeutic applications, though challenges include delivery, specificity, and unintended immune activation. Endogenous dsRNA and dsRNA produced by viruses remain central to understanding host–pathogen interactions.