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 journalArticle

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 languageEnglish (US)
Pages (from-to)144-150
Number of pages7
JournalNature Structural and Molecular Biology
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2010

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Djuranovic, S., Zinchenko, M. K., Hur, J. K., Nahvi, A., Brunelle, J. L., Rogers, E. J., & Green, R. (2010). Allosteric regulation of Argonaute proteins by miRNAs. Nature Structural and Molecular Biology, 17(2), 144-150. https://doi.org/10.1038/nsmb.1736