Structural basis for the self-chaperoning function of an RNA collapsed state.
Prior to folding to a native functional structure, many large RNAs form conformationally collapsed states. Formation of the near-native collapsed state for the bI5 group I intron RNA plays an obligatory role in self-chaperoning assembly with its CBP2 protein cofactor by preventing formation of stable, misassembled complexes. We show that the collapsed state is essential because CBP2 assembles indiscriminately with the bI5 RNA in any folding state to form long-lived complexes. The most stable protein interaction site in the expanded state-CBP2 complex overlaps, but is not identical to, the native site. Folding to the collapsed state circumvents two distinct misassembly events: inhibitory binding by multiple equivalents of CBP2 and formation of bridged complexes in which CBP2 straddles cognate and noncognate RNAs. Strikingly, protein-bound sites in the expanded state RNA complex are almost the inverse of native RNA-RNA and RNA-protein interactions, indicating that folding to the collapsed state significantly reduces the fraction of RNA surfaces accessible for misassembly. The self-chaperoning function for the bI5 collapsed state is likely to be conserved in other ribonucleoproteins where a protein cofactor binds tightly at a simple RNA substructure or has an RNA binding surface composed of multiple functional sites.
Garcia
Ivelitza
I
Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA.
Weeks
Kevin M
KM
D001483:Base Sequence; D001667:Binding, Competitive; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism
C116167:GIR1 ribozyme; D018832:Molecular Chaperones; D016337:RNA, Catalytic; D012261:Ribonucleoproteins