Fig. 2
From: Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers
Binding of splicing modifiers to RNP complex. a Binding of three compounds (SMN-C5/active, SMN-C7/inactive, and NVS-SM1) to the RNA duplex formed by the 5′ss and the 5-end of U1 snRNA was analyzed by solution-state1H NMR. The chemical-shift perturbations (CSP) of the H5-H6 protons of the pyrimidine bases are plotted as a function of the sequence. SMN-C5, but not SMN-C7 or NVS-SM1 binding to the RNA duplex was observed preferentially upstream of the pseudouridine pair in the region where the last adenine of exon 7 is bulged out, a hotspot highlighted for its ability to lower the splicing efficiency of SMN exon 7. b Cross-eyed stereo view of a NMR-guided model of the U1-5′ss RNA duplex in which U1-C zinc finger domain was modeled at the same interface as in the structure of U1 snRNP26, 27. In this model, protons strongly affected upon addition of SMN-C5 are represented by red beads, all of which define the binding interface of SMN-C5, located in the major groove of the RNA helix, whereas U1-C binds the minor groove. The molecule SMN-C5 is represented by the pink hexagon. Both binding interfaces are located on opposite sites, around the invariant GU motif of the 5′ss. The sequence of the RNA is given at the top of the figure. The U1 snRNA-derived oligonucleotide, the 5′ss, and U1-C are colored in blue, green, and orange, respectively
