Role of the snRNAs in spliceosomal active site

Abstract

The spliceosome, the ribonucleoprotein assembly that removes the intervening sequences from pre-mRNAs through splicing, is one of the most complex cellular machines. In humans it is composed of -150 proteins and five RNAs (snRNAs). One of the snRNAs, U6, contains sequences analogous to all the RNA elements that form the active site of the group II introns, ribozymes that perform a splicing reaction mechanistically identical to spliceosomal splicing. Interestingly, U6 is the only snRNA that is indispensable for splicing and in vitro, in complex with another snRNA, it can catalyze a primordial splicing reaction in the absence of all other spliceosomal factors. On the other hand, discovery of an RNase H-like domain in a spliceosomal protein that is closely associated with splice sites suggests that proteins may be involved in formation of the active site. Thus, whether the spliceosome is an RNA or RNA-protein catalyst remains uncertain.