The Role of snRNAs in Spliceosomal Catalysis - Progress in Molecular Biology and Translational Science - page 210

WhileRNAs can perform the above-mentioned interactions with ease and
evenmore effectively than proteins, proteins seemto have a catalytic advantage
over RNA, at least based on comparison of natural ribozymes and protein
enzymes. 84 Thus, a remaining question is whether the catalytic activity that
snRNAs demonstrate in isolation directly corresponds to their functionwithin
the spliceosomes in the presence of the spliceosomal proteins. In other words,
whether in the context of the spliceosomal active site, the snRNAs still supply
all or the majority of the functional groups involved in formation of the active
site remains unknown. Although a protein-only spliceosomal active site is
highly unlikely, it can be surmised that the spliceosomal proteins might pro-
vide functional groups in the active site. Although it has been shown that
snRNAs can form an active site capable of catalyzing a two-step splicing reac-
tion in the absence of proteins, 79 it is possible that in the spliceosomal active site
a protein functional group is added to the active site to assist in improving
the rate of the reaction. Alternatively, a protein functional group may replace
one or more of RNA functional group that participates in the formation of
the active site in the absence of proteins. These two scenarios might explain
the much higher rate of spliceosomal catalysis compared to protein-free,
snRNA-based splicing catalysis. Another alternative is that proteins, without
direct participation in catalysis, may assist the RNAs in forming an optimal
active site by contributing to productive positioning of the RNA functional
groups or assisting in proper positioning of the splicing substrates in the active
site. In these scenarios, the active site remains RNA based, but is heavily but-
tressed by proteins that allow it to be optimally functional, as has been observed
for other natural ribozymes (for a review, see ref. 83 ).
9. THE ROLE OF PROTEINS IN THE SPLICEOSOMAL
CATALYTIC CORE
Comparing the size of snRNAs with the much larger group II introns
raises the possibility that several group II intron domains may have been rep-
laced by proteins in the spliceosomes during evolution, giving rise to the
modern ribonucleoprotein (RNP) eukaryotic splicing machines. Although
no one-to-one correspondence yet exists, it is easily possible to identify
spliceosomal proteins that perform a function mediated by RNA elements
in group II introns. For example, a number of U2-associated proteins func-
tion in initiating and stabilizing the U2 snRNA-branch site interaction
( Fig. 6.3 ). 5,85 In group II introns, the U2 equivalent (part of domain VI)
is covalently linked to the branch site via a hyperstable hairpin loop in an