The spliceosome, the ribonucleoprotein complex that removes introns from precursor messenger RNAs, is thought to undergo conformational changes between two alternative states to catalyze the two steps of the splicing reaction, a model that resembles ribosomal transfer RNA decoding. Following very different strategies, two papers provide new insights into how core components of the spliceosome and regulatory factors containing arginine/serine-rich domains with RNA chaperone activity can facilitate these conformational changes.