Hierarchical Rules for Argonaute Loading in Drosophila

Benjamin Czech, Rui Zhou, Yaniv Erlich, Julius Brennecke, Richard Binari, Christians Villalta, Assaf Gordon, Norbert Perrimon, Gregory J. Hannon

Research output: Contribution to journalArticle

Abstract

Drosophila Argonaute-1 and Argonaute-2 differ in function and small RNA content. AGO2 binds to siRNAs, whereas AGO1 is almost exclusively occupied by microRNAs. MicroRNA duplexes are intrinsically asymmetric, with one strand, the miR strand, preferentially entering AGO1 to recognize and regulate the expression of target mRNAs. The other strand, miR*, has been viewed as a byproduct of microRNA biogenesis. Here, we show that miR*s are often loaded as functional species into AGO2. This indicates that each microRNA precursor can potentially produce two mature small RNA strands that are differentially sorted within the RNAi pathway. miR* biogenesis depends upon the canonical microRNA pathway, but loading into AGO2 is mediated by factors traditionally dedicated to siRNAs. By inferring and validating hierarchical rules that predict differential AGO loading, we find that intrinsic determinants, including structural and thermodynamic properties of the processed duplex, regulate the fate of each RNA strand within the RNAi pathway.

Original languageEnglish (US)
Pages (from-to)445-456
Number of pages12
JournalMolecular Cell
Volume36
Issue number3
DOIs
Publication statusPublished - Nov 13 2009
Externally publishedYes

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Keywords

  • PROTEINS
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Czech, B., Zhou, R., Erlich, Y., Brennecke, J., Binari, R., Villalta, C., ... Hannon, G. J. (2009). Hierarchical Rules for Argonaute Loading in Drosophila. Molecular Cell, 36(3), 445-456. https://doi.org/10.1016/j.molcel.2009.09.028