FUNCTIONAL-GROUP SUBSTITUTIONS OF THE BRANCHPOINT ADENOSINE IN A NUCLEAR PRE-MESSENGER-RNA AND A GROUP-II INTRON

Splicing of nuclear mRNA precursors (pre-mRNAs) takes place in the spl iceosome, a large and complex ribonucleoprotein. Nuclear pre-mRNA spli cing and group II intron self-splicing occur by a chemically identical pathway involving recognition of a specific branchpoint adenosine and nucleophilic activation of its 2'-hydroxyl group. The chemical simila rity between these two splicing reactions, as well as other considerat ions, have suggested that the catalytic core of the spliceosome and gr oup II introns may be related. Here we test this hypothesis by analyzi ng splicing and RNA branch formation of a pre-mRNA and a group II intr on in which the branchpoint adenosine was substituted with purine base analogues. We find that replacement of the branchpoint adenosine with either of two modified adenosine analogues or guanosine leads to rema rkably similar patterns of splicing and RNA branch formation in the tw o systems.