A collapsed state functions to self-chaperone RNA folding into a native ribonucleoprotein complex

Most large RNAs achieve their active, native structures only as complexes w ith one or more cofactor proteins. By varying the Mg2+ concentration, the c atalytic core of the bI5 group I intron RNA can be manipulated into one of three states, expanded, collapsed or native, or into balanced equilibria be tween these states. Under near-physiological conditions, the bI5 RNA folds rapidly to a collapsed but non-native state. Hydroxyl radical footprinting demonstrates that assembly with the CBP2 protein cofactor chases the RNA fr om the collapsed state to the native state. In contrast, CBP2 also binds to the RNA in the expanded state to form many non-native Interactions. This s tructural picture is reinforced by functional splicing experiments showing that RNA in an expanded state forms a non-productive, kinetically trapped c omplex with CBP2, Thus, rapid folding to the collapsed state functions to s elf-chaperone bI5 RNA folding by preventing premature interaction with its protein cofactor. This productive, self-chaperoning role for RNA collapsed states may be especially important to avert misassembly of large multi-comp onent RNA-protein machines in the cell.