A UHM-ULM interface contributes to the pre-mRNA splicing functions of U2AF2 and SF3B1

Abstract

Recognition of the 3′ splice site is an essential, regulated stage of spliceosome assembly. The U2AF homology motif (UHM) of U2AF2 binds a U2AF ligand motif (ULM) of the SF1 subunit at the 3′ splice site of the early-stage spliceosome. Subsequently, SF1 is displaced by SF3B1, a subunit of the U2 small nuclear ribonucleoprotein particle that contains five ULMs. However, the nature of the SF3B1-U2AF2 interface and its importance for pre-mRNA splicing remain unknown. To address this knowledge gap, we determined the crystal structure of the U2AF2 UHM bound to the SF3B1 ULM site at 1.8 Å resolution.