Allosteric regulation of Argonaute proteins by miRNAs

Sergej Djuranovic; Michelle Kim Zinchenko; Junho K. Hur; Ali Nahvi; Julie L. Brunelle; Elizabeth J. Rogers; Rachel Green

doi:10.1038/nsmb.1736

Allosteric regulation of Argonaute proteins by miRNAs

Sergej Djuranovic, Michelle Kim Zinchenko, Junho K. Hur, Ali Nahvi, Julie L. Brunelle, Elizabeth J. Rogers, Rachel Green

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

Small interfering RNAs (siRNAs) and microRNAs (miRNAs) bind to Argonaute (AGO) family proteins to form a related set of effector complexes that have diverse roles in post-transcriptional gene regulation throughout the eukaryotic lineage. Here sequence and structural analysis of the MID domain of the AGO proteins identified similarities with a family of allosterically regulated bacterial ligand-binding domains. We used in vitro and in vivo approaches to show that certain AGO proteins (those involved in translational repression) have conserved this functional allostery between two distinct sites, one involved in binding miRNA-target duplex and the other in binding the 5′ cap feature (m⁷GpppG) of eukaryotic mRNAs. This allostery provides an explanation for how miRNA-bound effector complexes may avoidindiscriminate repressive action (mediated through binding interactions with the cap) before full target recognition.

Original language	English
Pages (from-to)	144-150
Number of pages	7
Journal	Nature Structural and Molecular Biology
Volume	17
Issue number	2
DOIs	https://doi.org/10.1038/nsmb.1736
State	Published - Feb 2010

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title = "Allosteric regulation of Argonaute proteins by miRNAs",

abstract = "Small interfering RNAs (siRNAs) and microRNAs (miRNAs) bind to Argonaute (AGO) family proteins to form a related set of effector complexes that have diverse roles in post-transcriptional gene regulation throughout the eukaryotic lineage. Here sequence and structural analysis of the MID domain of the AGO proteins identified similarities with a family of allosterically regulated bacterial ligand-binding domains. We used in vitro and in vivo approaches to show that certain AGO proteins (those involved in translational repression) have conserved this functional allostery between two distinct sites, one involved in binding miRNA-target duplex and the other in binding the 5′ cap feature (m7GpppG) of eukaryotic mRNAs. This allostery provides an explanation for how miRNA-bound effector complexes may avoidindiscriminate repressive action (mediated through binding interactions with the cap) before full target recognition.",

author = "Sergej Djuranovic and Zinchenko, {Michelle Kim} and Hur, {Junho K.} and Ali Nahvi and Brunelle, {Julie L.} and Rogers, {Elizabeth J.} and Rachel Green",

note = "Funding Information: We thank S. Dorner for early contributions to the project, E. Izaurralde (Max Planck Institute) for providing the luciferase reporter constructs, H. Zaher (Johns Hopkins Univ. School of Medicine) for mRNA constructs used in filter binding assays, and J. Mendell, G. Seydoux, J. Lorsch, L. Cochella and H. Zaher for helpful comments on the manuscript. J.K.H. was supported by The Samsung Foundation of Culture. The project was supported by funding from the Howard Hughes Medical Institute.",

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AU - Rogers, Elizabeth J.

AU - Green, Rachel

N1 - Funding Information: We thank S. Dorner for early contributions to the project, E. Izaurralde (Max Planck Institute) for providing the luciferase reporter constructs, H. Zaher (Johns Hopkins Univ. School of Medicine) for mRNA constructs used in filter binding assays, and J. Mendell, G. Seydoux, J. Lorsch, L. Cochella and H. Zaher for helpful comments on the manuscript. J.K.H. was supported by The Samsung Foundation of Culture. The project was supported by funding from the Howard Hughes Medical Institute.

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AB - Small interfering RNAs (siRNAs) and microRNAs (miRNAs) bind to Argonaute (AGO) family proteins to form a related set of effector complexes that have diverse roles in post-transcriptional gene regulation throughout the eukaryotic lineage. Here sequence and structural analysis of the MID domain of the AGO proteins identified similarities with a family of allosterically regulated bacterial ligand-binding domains. We used in vitro and in vivo approaches to show that certain AGO proteins (those involved in translational repression) have conserved this functional allostery between two distinct sites, one involved in binding miRNA-target duplex and the other in binding the 5′ cap feature (m7GpppG) of eukaryotic mRNAs. This allostery provides an explanation for how miRNA-bound effector complexes may avoidindiscriminate repressive action (mediated through binding interactions with the cap) before full target recognition.

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Allosteric regulation of Argonaute proteins by miRNAs

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