| RNA Tertiary Folding
Group II introns have provided a valuable paradigm for studying the RNA folding problem, which can be framed in the
following way: How does a particular sequence of RNA adopt a unique three-dimensional shape, and what is the pathway by
which it gets there? Most RNAs have difficulty reaching the proper "native" tertiary structure because they
become locked into stable, misfolded structures. Group II introns appear to be different. Despite its large size (880
nts), the yeast ai5γ group IIB intron folds directly and correctly to the proper three-dimensional structure under
ionic conditions that promote ribozyme activity in-vitro. The ai5γ folding pathway involves the sequential formation of
intermediate structures that gradually build up the catalytically active molecule. The first event along the folding
pathway is the collapse and assembly of intron Domain 1, which provides the scaffold for subsequent assembly events.
Remarkably, the rate-limiting event in D1 collapse is formation of the "folding control element", which is a
small junction motif in the center of the domain. Once this motif has adopted the proper configuration, a series of
long-range tertiary contacts within D1 lock this domain into the active conformation. D1 collapse is then rapidly
followed by the docking of D5 and D3, which combine to form the intron active-site. In-vivo, this process is facilitated
by the action of bound proteins, which are likely to serve multiple roles in facilitating D1 collapse and stabilization of
the final native state (Pyle et al, TIBS 2007; Waldsich & Pyle, JMB 2007).