A Guanosine-Centric Mechanism for RNA Chaperone Function

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Science  12 Apr 2013:
Vol. 340, Issue 6129, pp. 190-195
DOI: 10.1126/science.1230715

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Simply Folding

RNA chaperones simplify what would otherwise be complex and slow RNA folding events. Grohman et al. (p. 190, published online 7 March) show that the Moloney murine leukemia virus (MuLV) nucleocapsid (NC) protein, which chaperones MuLV RNA dimerization promotes MuLV RNA folding by binding to exposed guanosine bases and destabilizing strong guanosine interactions. With base-pairs being rendered roughly of the same energy, RNA assembly pathways are simplified, promoting proper folding.


RNA chaperones are ubiquitous, heterogeneous proteins essential for RNA structural biogenesis and function. We investigated the mechanism of chaperone-mediated RNA folding by following the time-resolved dimerization of the packaging domain of a retroviral RNA at nucleotide resolution. In the absence of the nucleocapsid (NC) chaperone, dimerization proceeded through multiple, slow-folding intermediates. In the presence of NC, dimerization occurred rapidly through a single structural intermediate. The RNA binding domain of heterogeneous nuclear ribonucleoprotein A1 protein, a structurally unrelated chaperone, also accelerated dimerization. Both chaperones interacted primarily with guanosine residues. Replacing guanosine with more weakly pairing inosine yielded an RNA that folded rapidly without a facilitating chaperone. These results show that RNA chaperones can simplify RNA folding landscapes by weakening intramolecular interactions involving guanosine and explain many RNA chaperone activities.

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