Three dimensional structure and sequence homology determine splicing sites in eukaryotic precursor RNA

About two years ago it was first shown that in the human virus, Adenovirus 2, non-consecutive DNA segments were next to each other on the messenger RNA (mRNA) chain. Further investigation showed that the newly synthesized precursor mRNA contains the same, full DNA sequence. Only at a later stage a section (or sections) of the messenger loops out and splicing, followed by ligation (joining) of the ends, takes place. Since then it was shown that most eukaryotic mRNAs undergo splicing. We suggest here a new structural approach for the splicing phenomenon and location of splicing sites. It emphasizes spatial proximity, orientation and stability incurred by secondary and tertiary structure around and sequence homology at the splicing sites. Based on the above spatial considerations, two and three dimensional models were built for the known splicing sites in the small mRNA of the primate virus SV40, denoted 16S mRNA, which is transcribed late in the viral life cycle and for the variable region of the mouse immunoglobulin light chain. Models similar to the former were also constructed for other regions of SV40 and specific predictions were made for splicings in the SV40 late 19S and for the early synthesized mRNAs. These were recently verified.