Figure 3. Model for the regulation of Brr2 by Prp8. Model for the regulation of Brr2 by the Prp8 RH and Jab1 domains during pre-mRNA splicing. Red lines, inhibitory effects; green arrows, stimulatory effects. (I) Inhibited state in the U4/U6•U5 tri-snRNP and the B complex achieved by competitive binding of a single-stranded U4 snRNA region upstream of stem I (thick black line) via the RH domain (Mozaffari-Jovin et al., 2012) and by blocking the Brr2 RNA-binding tunnel and disrupting N-terminal cassette (NC)—C-terminal cassette (CC) interactions via the Jab1 domain. (II) State after release of U4 snRNA from RH. Brr2 is still blocked via the Jab1 domain. The conserved U6 ACAGAG box (thick gray line) has taken over base pairing of the 5′ ss from U1 snRNA. (III) Brr2 stimulation during spliceosome catalytic activation via the Jab1 domain and by direct interaction of the NC with CC.²⁷ Magenta arrow—movement of Brr2 on U4 snRNA. (IV) The Jab1 domain may again block Brr2 activity at some point after spliceosome catalytic activation, although there is presently no direct experimental evidence for the direct inhibition of Brr2 during the later stages of splicing. Adapted from reference 42.