The Cwc2/Ecm2/Isy1 interaction network and structure of human RBM22. (A) A large number of splicing factors interact with Cwc2, Ecm2, and/or Isy1 suggesting that these proteins form a network hub for modulating spliceosome activity. In this model, regulatory signals could flow into the hub from the NTC and NTC-related proteins and outwards to the spliceosome active site consisting of the intron, Prp8, and U2/U6 snRNAs. (B) Two views of the cryo-EM structure of RBM22 from a human C complex spliceosome. Domains of RBM22 are noted and intronic RNA downstream from the 5′ SS is shown in black spacefill. Note that RBM22 completely encircles the RNA. Structure from 6EXN.pdb. (C) Hypothetical model for formation of the structure shown in panel B. The RRM domain of RBM22 could make transient contact with human U2 stem IIb to allow for docking of the intron and subsequent wrapping. Structures in panels B and C are from 5YZG.pdb. The hypothetical model in panel C was created using PyMol.
