The Spliceosome: The Ultimate RNA Chaperone and Sculptor

The spliceosome, one of the most complex machineries of eukaryotic cells, removes intronicsequences from primary transcriptsto generate functional messenger and long noncoding RNAs (lncRNA). Genetic, biochemical, and structural data reveal that the spliceosomeis an RNA-based enzyme. Striking mechanistic and structural similaritiesstrongly argue that pre-mRNA intronsoriginated from self-catalytic group II ribozymes. However, in the spliceosome, protein components organize and activate the catalytic-site RNAs, and recognize and pair together splice sites at intronboundaries. The spliceosomeis a dynamic, reversible, and flexible machine that chaperones small nuclear (sn) RNAs and a variety of pre-mRNA sequences into conformations that enable intronremoval. This malleabilitylikely contributes to the regulation of alternative splicing, a prevalent process contributing to cell differentiation, homeostasis, and disease.