Structural studies of the U12-dependent spliceosome

Pre-mRNA splicing is a fundamental cellular process that affects gene expression. It involves the precise excision of non-coding introns from pre-mRNA, a reaction catalyzed by the spliceosome, a highly dynamic and complex molecular machinery. The spliceosome comprises more than hundred proteins and undergoes extensive compositional and conformational rearrangements throughout the splicing cycle . In human cells, majority of introns are processed by so-called major, U2-dependent spliceosome. A small proportion of introns in essential genes are processed by a non-canonical U12-dependent splicesome (minor spliceosome). Our research focuses on obtaining insights into minor spliceosome function via structural analysis by single particle cryoEM and biochemistry.