title: Why Argonaute is needed to make microRNA target search fast and reliable.
abstract: MicroRNA (miRNA) interferes with the translation of cognate messenger RNA (mRNA) by finding, preferentially binding, and marking it for degradation. To facilitate the search process, Argonaute (Ago) proteins come together with miRNA, forming a dynamic search complex. In this review we use the language of free-energy landscapes to discuss recent single-molecule and high-resolution structural data in the light of theoretical work appropriated from the study of transcription-factor search. We suggest that experimentally observed internal states of the Ago-miRNA search complex may have the explicit biological function of speeding up search while maintaining specificity.
authors.affiliation: Kavli Institute of NanoScience and Department of BioNanoScience, Delft University of Technology, Delft, 2629HZ, The Netherlands.
authors.forename: Misha
authors.initials: M
authors.lastname: Klein
authors.affiliation: Kavli Institute of NanoScience and Department of BioNanoScience, Delft University of Technology, Delft, 2629HZ, The Netherlands.
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Chandradoss
authors.affiliation: Kavli Institute of NanoScience and Department of BioNanoScience, Delft University of Technology, Delft, 2629HZ, The Netherlands. Electronic address: s.m.depken@tudelft.nl.
authors.forename: Martin
authors.initials: M
authors.lastname: Depken
authors.affiliation: Kavli Institute of NanoScience and Department of BioNanoScience, Delft University of Technology, Delft, 2629HZ, The Netherlands. Electronic address: c.joo@tudelft.nl.
authors.forename: Chirlmin
authors.initials: C
authors.lastname: Joo
mesh_terms: D060565:Argonaute Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D004058:Diffusion; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013816:Thermodynamics
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Argonaute; FRET; Free-energy landscape; Lateral diffusion; MicroRNA target prediction; RNA silencing; Search stability paradox; Single molecule; Target Search; Theoretical model; miRNA