Mechanism of 5ʹ splice site transfer for human spliceosome activation

Abstract

Creation of the splicing catalytic center The catalytic center of the fully assembled, precatalytic pre–B spliceosome is not yet formed, even though all the pieces are present in this complex. Charenton et al. solved the structures of the human pre–B complex, providing detailed mechanistic insights into how the helicase Prp28 transfers the 5′ splice site of the messenger RNA precursor from U1 small nuclear ribonucleoprotein (snRNP) to U6 snRNA. The pairing of the 5′ splice site with U6 induces a series of conformational changes that triggers the relocation of Brr2 helicase and loading of U4 snRNA to the helicase active site. This leads to unwinding of the U4/U6 snRNA duplex and allows U6 to fold and pair with U2 to create the spliceosome active site. Science , this issue p. 362