GSBS Student Publications


Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology



Document Type


Medical Subject Headings

Animals; Drosophila melanogaster; Endoribonucleases; *Gene Expression Regulation; Genes, Insect; Hela Cells; Humans; Phosphates; RNA Interference; RNA, Double-Stranded; RNA, Small Interfering; Ribonuclease III


Life Sciences | Medicine and Health Sciences


In Drosophila, two features of small interfering RNA (siRNA) structure--5' phosphates and 3' hydroxyls--are reported to be essential for RNA interference (RNAi). Here, we show that as in Drosophila, a 5' phosphate is required for siRNA function in human HeLa cells. In contrast, we find no evidence in flies or humans for a role in RNAi for the siRNA 3' hydroxyl group. Our in vitro data suggest that in both flies and mammals, each siRNA guides endonucleolytic cleavage of the target RNA at a single site. We conclude that the underlying mechanism of RNAi is conserved between flies and mammals and that RNA-dependent RNA polymerases are not required for RNAi in these organisms.

Rights and Permissions

Citation: Mol Cell. 2002 Sep;10(3):537-48.

Related Resources

Link to Article in PubMed

Journal Title

Molecular cell

PubMed ID