Splicing of an intervening sequence by protein-free human snRNAs

Significant structural and mechanistic similarities between the spliceosomal snRNAs and catalytically critical domains of self-splicing group II introns have led to the hypothesis that the spliceosomes and group II introns may be evolutionarily related. We have previously shown that in vitro-transcribed, protein-free U6 and U2 snRNAs can catalyze a two-step splicing reaction in trans on two short RNA oligonucleotides that is identical to the splicing reactions performed by many self-splicing group II introns. Here we show that the same two snRNAs can perform splicing in cis by removal of an intervening sequence from a model substrate. These results prove that the protein-free snRNAs are competent to perform splicing on pre-mRNAs and further strengthen the possibility of an evolutionary relationship to group II introns.