Extended Data Figure 4: Interactions of spliceosomal proteins with the U6 snRNA in the C* complex.

a, Overview of the location of various proteins and functionally important regions of the U6 and U2 snRNAs in the C* complex. b, c, Close up of the fit of G10/BUD31, the PRP8 NTD1, and RBM22, as well as the U6 5′ stem loop, into the EM density map of C*. d, Comparison of the domain structure of human RBM22 with that of its apparent homologues in yeast, Cwc2 and Ecm2. e, Comparison of the organization of homologous domains between RBM22, and Ecm2 and Cwc2, in the human C* and S. cerevisiae C complexes. The middle and right diagrams show different slices of the C complex EM density. Some regions of human RBM22 that are homologous to regions of the S. cerevisiae Cwc2 and Ecm2 proteins, are located near the U6 ISL in the human C* complex, similar to the situation in the S. cerevisiae C complex. For example, the N-terminal part of RBM22, comprising two zinc-finger domains that are homologous to those present in S. cerevisiae Ecm2, could be fit into a density element close to G10/BUD31, at a position similar to that in the S. cerevisiae C complex (and S. pombe ILS, not shown). The third zinc-finger domain of RBM22 (homologous to Cwc2) is located close to the 5′ stem loop of U6 snRNA. The RRM domain of RBM22 (homologous to the RRM of Cwc2) fits into a less well-defined density element close to PPIL1, aquarius, and Skip, consistent with protein crosslinking data (Supplementary Table 2). Thus, the RRM of RBM22 is located at a different position compared to that of its likely yeast homologue (Cwc2/Cwf2) in the yeast spliceosomes.