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 (m(7)GpppG) of eukaryotic mRNAs. This allostery provides an explanation for how miRNA-bound effector complexes may avoid indiscriminate repressive action (mediated through binding interactions with the cap) before full target recognition.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Sergej
authors.initials: S
authors.lastname: Djuranovic
authors.forename: Michelle Kim
authors.initials: MK
authors.lastname: Zinchenko
authors.forename: Junho K
authors.initials: JK
authors.lastname: Hur
authors.forename: Ali
authors.initials: A
authors.lastname: Nahvi
authors.forename: Julie L
authors.initials: JL
authors.lastname: Brunelle
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Rogers
authors.forename: Rachel
authors.initials: R
authors.lastname: Green
mesh_terms: D000494:Allosteric Regulation; D039642:Eukaryotic Initiation Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012315:RNA Caps / Q000378:metabolism*
chemical_list: D039642:Eukaryotic Initiation Factors; D035683:MicroRNAs; D012315:RNA Caps