Involvement of a GNRA tetraloop in long-range RNA tertiary interactions

Abstract

Terminal loops with a GNRA consensus sequence are widespread in RNA. It has been suggested that these loops act as "anchors" during tertiary folding, by interacting in a sequence-specific way with helices at distant locations along the molecule. We now show that a GUGA loop changes state upon disruption of the tertiary architecture of a self-splicing group I intron. Successful replacement of the postulated loop-helix contact by classical base-pairing points to binding of the loop into the shallow (minor) groove of the helix, as also indicated by partial restoration of ribozyme stability upon a specific double nucleotide substitution.