SAP30BP interacts with RBM17/SPF45 to promote splicing in a subset of human short introns

• Published in: Cell reports (Cambridge) Vol. 42; no. 12; p. 113534
• Main Authors: Fukumura, Kazuhiro, Sperotto, Luca, Seuß, Stefanie, Kang, Hyun-Seo, Yoshimoto, Rei, Sattler, Michael, Mayeda, Akila
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-12-2023
• Subjects: Humans; Introns - genetics; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; polypyrimidine tract; pre-mRNA splicing; RBM17; Ribonucleoprotein, U2 Small Nuclear - genetics; RNA Precursors - metabolism; RNA Splicing - genetics; RNA Splicing Factors - genetics; RNA Splicing Factors - metabolism; SAB30BP; SF3B1; SF3b155; short intron; SPF45; Spliceosomes - metabolism; Splicing Factor U2AF - genetics; Splicing Factor U2AF - metabolism; Transcription Factors - metabolism; U2 snRNP; U2AF heterodimer; U2AF-homology motif; UHM; UHM-ligand motif; ULM; RBM17; U2AF-homology motif; U2 snRNP; U2AF heterodimer; short intron; UHM-ligand motif; SAB30BP; ULM; CP: Molecular biology; SF3b155; UHM; SPF45; SF3B1; pre-mRNA splicing; polypyrimidine tract
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113534

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.
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•RBM17 (SPF45) is a splicing factor required for a subset of human short introns•SAP30BP is an essential cofactor, which interacts with RBM17 via UHM-ULM binding•RBM17 forms a weak complex with SAP30BP before its binding with SF3B1 in U2 snRNP•RBM17-SAP30BP complex supports RBM17 to be recruited to active phosphorylated SF3B1
Fukumura et al. describe a general splicing mechanism in a subset of human short introns with truncated polypyrimidine tracts. This splicing reaction is mediated by the intermediary RBM17-SAP30BP complex, instead of the known U2AF heterodimer. SAP30BP binding to RBM17 may support RBM17 association with active phosphorylated SF3B1 in U2 snRNP.