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

doi:10.1016/j.molcel.2009.09.028

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 journal › Article › peer-review

198 Scopus citations

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 language	English (US)
Pages (from-to)	445-456
Number of pages	12
Journal	Molecular cell
Volume	36
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2009.09.028
State	Published - Nov 13 2009
Externally published	Yes

Keywords

PROTEINS
RNA

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2009.09.028

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title = "Hierarchical Rules for Argonaute Loading in Drosophila",

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.",

keywords = "PROTEINS, RNA",

author = "Benjamin Czech and Rui Zhou and Yaniv Erlich and Julius Brennecke and Richard Binari and Christians Villalta and Assaf Gordon and Norbert Perrimon and Hannon, {Gregory J.}",

note = "Funding Information: We thank R. Carthew, Q. Liu, P. Jin, H. Siomi, P.D. Zamore, E. Lai, and the Bloomington Stock Center for fly strains. We are grateful to M. Kudla, O. Tam, M. Rooks, D. McCombie, and C. Pitsouli for technical and computational contributions. We thank R. Davis and J. Dover for kindly sequencing two Solexa libraries at University of Colorado, Denver. B.C. is supported by a PhD fellowship from the Boehringer Ingelheim Fonds. R.Z. is a Special Fellow of the Leukemia and Lymphoma Society. This work was supported in part by grants from the NIH to N.P. and G.J.H. and a gift from K.W. Davis (G.J.H.). N.P. and G.J.H. are investigators of the HHMI. ",

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doi = "10.1016/j.molcel.2009.09.028",

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T1 - Hierarchical Rules for Argonaute Loading in Drosophila

AU - Czech, Benjamin

AU - Zhou, Rui

AU - Erlich, Yaniv

AU - Brennecke, Julius

AU - Binari, Richard

AU - Villalta, Christians

AU - Gordon, Assaf

AU - Perrimon, Norbert

AU - Hannon, Gregory J.

N1 - Funding Information: We thank R. Carthew, Q. Liu, P. Jin, H. Siomi, P.D. Zamore, E. Lai, and the Bloomington Stock Center for fly strains. We are grateful to M. Kudla, O. Tam, M. Rooks, D. McCombie, and C. Pitsouli for technical and computational contributions. We thank R. Davis and J. Dover for kindly sequencing two Solexa libraries at University of Colorado, Denver. B.C. is supported by a PhD fellowship from the Boehringer Ingelheim Fonds. R.Z. is a Special Fellow of the Leukemia and Lymphoma Society. This work was supported in part by grants from the NIH to N.P. and G.J.H. and a gift from K.W. Davis (G.J.H.). N.P. and G.J.H. are investigators of the HHMI.

PY - 2009/11/13

Y1 - 2009/11/13

N2 - 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.

AB - 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.

KW - PROTEINS

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ER -

Hierarchical Rules for Argonaute Loading in Drosophila

Abstract

Keywords

ASJC Scopus subject areas

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