Abstract
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 U2 auxiliary 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 nuclear magnetic resonance analyses demonstrate that a U2AF-homology motif (UHM) in RBM17 binds directly to a newly identified UHM-ligand motif in SAP30BP. We show that this RBM17-SAP30BP interaction is required to specifically recruit RBM17 to phosphorylated SF3B1 (SF3b155), a U2 small nuclear ribonucleoprotein (U2 snRNP) component in active spliceosomes. We propose a mechanism for splicing in a subset of short introns, in which SAP30BP guides RBM17 in the assembly of active spliceosomes.
Original language | English |
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Article number | 113534 |
Journal | Cell Reports |
Volume | 42 |
Issue number | 12 |
DOIs | |
State | Published - 26 Dec 2023 |
Externally published | Yes |
Keywords
- CP: Molecular biology
- RBM17
- SAB30BP
- SF3B1
- SF3b155
- SPF45
- U2 snRNP
- U2AF heterodimer
- U2AF-homology motif
- UHM
- UHM-ligand motif
- ULM
- polypyrimidine tract
- pre-mRNA splicing
- short intron