A mechanistic model for the two-step “hand-over” of the BS from SF1 to the U2snRNP. (Left) In the first step of the BS “hand-over” from SF1 to U2snRNP, SUGP1 is located near the BS through direct contacts with SF1 and U2AF2 and recruits the SF3B1-containing U2snRNP to the vicinity of the BS by directly contacting the hotspot region of the SF3B1 HD through two regions flanking its G-patch domain, which loops-out to activate DHX15. Then DHX15 “pulls” the pre-mRNA by helicase tracking into the RNA path of SF3B1 and displaces SF1 from the predefined BS, which becomes available for correct recognition by the p14 subunit of SF3B1 in the pre-A complex. (Right) In the second step of the hand-over, following the dissociation of SUGP1 from the complex, DDX46 is recruited to the U2snRNP by the same hotspot region previously occupied by SUGP1. DDX46 then unwinds the BSL of the U2snRNA to allow the formation of the U2-BS RNA duplex with a bulged BP-A, which is incorporated into the RNA channel of SF3B1 in the catalytically primed A-complex. (Figure modified from Zhang et al. 2019.)
