Structural studies of the pre-mRNA splicing complexes

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 (4). 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) (5). Due to its low cellular abundance minor spliceosome remains poorly characterised. Our research focuses on obtaining insights into minor spliceosome function via structural analysis by single particle cryoEM and biochemistry.