Abstract
Background: RNA interference (RNAi) and related pathways involving small interfering RNAs (siRNAs), microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs) regulate processes such as antiviral defense, genome surveillance, heterochromatin formation, and gene expression in animals, plants, and fungi. Studies on RNAi have revealed a two-step mechanism: (i) Degradation of dsRNA into small interfering RNAs (siRNAs), 21 to 25 nucleotides long, by an RNase III-like activity. (ii) The siRNAs join an RNase complex, RISC (RNA-induced silencing complex), which acts on the mRNA and degrades it.
Objective: Molecular structures of Dicer, Argonaute proteins, and RNA-bound complexes have offered insights into the underlying mechanisms of RNA-silencing pathways.
Methods: Sequence specific gene silencing using small interfering RNA (siRNA) is now being evaluated as a novel therapeutic strategy.
Results: Recently, promising data have been obtained from clinical trials for the treatment of respiratory syncytial virus and age-related macular degeneration. The exact mechanism of the RNAi pathways is still unclear.
Conclusion: Our review summarizes the RNAi pathways and the known functions of siRNAs, miRNAs, and piRNAs in lower and higher organisms (mostly focusing on mammals) and discusses the potential applications of RNAi.
Keywords: miRNAs, piRNAs, RNAi pathways, siRNAs, nucleotides, heterochromatin.
Graphical Abstract
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