FREQUENT USE OF THE SAME TERTIARY MOTIF BY SELF-FOLDING RNAS

We have identified an 11 nucleotide RNA motif, [CCUAAG...UAUGG], that is extraordinarily abundant in group I and group II self-splicing introns at sites known, or suspected from co-variation analysis, to interact with hairpin terminal loops with a GNRA consensus sequence. Base substitution experiments using a ribozyme-substrate system derived from a group I intron reveal that this motif interacts preferentially with GAAA terminal loops and binds them with remarkable affinity, compared with other known combinations of GNRA loops and matched targets. A copy of the [CCUAAG...UAUGG] motif which is present in domain I of many group II introns is shown to interact with the GAAA terminal loop that caps domain V. This is the first interaction to be identified between these two domains, whose mutual recognition is known to be necessary and sufficient for group II ribozymic activity. We conclude that interaction of [CCUAAG...UAUGG] with GAAA loops is one of the most common solutions used by nature to solve the problem of compacting and bringing together RNA structural domains.