ATP requirements and small interfering RNA structure in the RNA interference pathway
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Adenosine Triphosphate; Animals; Drosophila; *Gene Silencing; Models, Genetic; Phosphorylation; Proteins; *RNA Processing, Post-Transcriptional; RNA, Double-Stranded; RNA, Small Interfering; RNA, Untranslated
Life Sciences | Medicine and Health Sciences
We examined the role of ATP in the RNA interference (RNAi) pathway. Our data reveal two ATP-dependent steps and suggest that the RNAi reaction comprises at least four sequential steps: ATP-dependent processing of double-stranded RNA into small interfering RNAs (siRNAs), incorporation of siRNAs into an inactive approximately 360 kDa protein/RNA complex, ATP-dependent unwinding of the siRNA duplex to generate an active complex, and ATP-independent recognition and cleavage of the RNA target. Furthermore, ATP is used to maintain 5' phosphates on siRNAs. A 5' phosphate on the target-complementary strand of the siRNA duplex is required for siRNA function, suggesting that cells check the authenticity of siRNAs and license only bona fide siRNAs to direct target RNA destruction.
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Citation: Cell. 2001 Nov 2;107(3):309-21.
Nykanen, Antti; Haley, Benjamin; and Zamore, Phillip D., "ATP requirements and small interfering RNA structure in the RNA interference pathway" (2001). GSBS Student Publications. 909.