Abstract
SUMMARY Human pre-mRNA splicing requires the removal of introns with highly variable lengths, from tens to over a million nucleotides. Therefore, mechanisms of intron recognition and splicing are likely not universal. Recently, we reported that splicing in a subset of human short introns with truncated polypyrimidine tracts depends on RBM17 (SPF45), instead of the canonical splicing factor U2AF heterodimer. Here, we demonstrate that SAP30BP, a factor previously implicated in transcriptional control, is an essential splicing cofactor for RBM17. In vitro binding and NMR analyses demonstrate that a U2AF-homology motif (UHM) in RBM17 binds directly to a newly identified UHM-ligand motif (ULM) in SAP30BP. We show that this RBM17–SAP30BP interaction is required to specifically recruit RBM17 to phosphorylated SF3B1 (SF3b155), a U2 snRNP component in active spliceosomes. We propose a unique mechanism for splicing in a subset of short introns, in which SAP30BP guides RBM17 in the assembly of active spliceosomes.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵5 Lead contact
NMR/ITC data were updated in Figure 4 (Figure 5 in the first version).Supplementary Figure S2 (Figure S1 in the first version) was updated.
The list of retained introns in RBM17- and SAP30BP-knockdown HeLa cells were provided in Supplementary Table S1 (under separate PDF file). Minor modifications and corrections were applied in the text and figures.
