Splicing of pre-mRNA: mechanism, regulation and role in development

Abstract

Over the past year, significant progress has been made in the understanding of how RNA-binding factors may facilitate splice-site selection and spliceosome assembly, and confer fidelity to the pre-mRNA splicing reaction. In addition, a number of studies have revealed a complex network of RNA-RNA interactions in the spliceosome, strengthening the structural and functional parallels between nuclear pre-mRNA splicing and the self-splicing group I and group II introns. These new data further support the idea that pre-mRNA splicing occurs by RNA-mediated catalysis and illustrate quite dramatically the dynamic nature of conformational changes in the spliceosome cycle. With respect to tissue-specific pre-mRNA splicing, a number of studies have begun to illuminate mechanisms underlying control of splice-site selection and how so-called ‘general’ RNA-binding proteins, such as heterogeneous nuclear ribonucleoproteins, may be involved in determining different splicing patterns. Finally, an emerging theme involving the role of splicing in development is that differential transcriptional programs can be triggered in different cell types by alternative splicing patterns that generate transcription factor isoforms with different activities or DNA-binding specificities.