Structural basis of branch site recognition by the human spliceosome

Abstract

Intron recognition in the spotlight Excision of noncoding introns from pre–messenger RNAs is catalyzed by the spliceosome, a large RNA-protein complex that recognizes specific sequences at the exon-intron boundaries (splice sites). These sequences are highly degenerate in humans, and it has remained elusive how they are recognized by the spliceosome. Tholen et al . report a series of high-resolution structures of the human U2 small nucleolar ribonucleoprotein, the component of the spliceosome that recognizes branch sites. The structures explain how SF3B6 helps to stabilize the branch helix in the absence of extensive sequence complementarity. A newly identified spliceosome assembly intermediate suggests a mechanism for fidelity control of branch site recognition. —DJ