7P08

Solution structure of the human SF3A1 ubiquitin-like domain

Summary for 7P08

• Entry DOI: 10.2210/pdb7p08/pdb
• Related: 1ZKH
• NMR Information: BMRB: 34643
• Descriptor: Isoform 1 of Splicing factor 3A subunit 1 (1 entity in total)
• Functional Keywords: spliceosome, u2 snrnp, sf3a, ubiqutin-like domain, splicing
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 10238.93

Authors

de Vries, T.,Campagne, S.,Allain, F.H.T. (deposition date: 2021-06-29, release date: 2022-02-09, Last modification date: 2024-06-19)

Primary citation

de Vries, T.,Martelly, W.,Campagne, S.,Sabath, K.,Sarnowski, C.P.,Wong, J.,Leitner, A.,Jonas, S.,Sharma, S.,Allain, F.H.
Sequence-specific RNA recognition by an RGG motif connects U1 and U2 snRNP for spliceosome assembly.
Proc.Natl.Acad.Sci.USA, 119:-, 2022

PubMed Abstract: In mammals, the structural basis for the interaction between U1 and U2 small nuclear ribonucleoproteins (snRNPs) during the early steps of splicing is still elusive. The binding of the ubiquitin-like (UBL) domain of SF3A1 to the stem-loop 4 of U1 snRNP (U1-SL4) contributes to this interaction. Here, we determined the 3D structure of the complex between the UBL of SF3A1 and U1-SL4 RNA. Our crystallography, NMR spectroscopy, and cross-linking mass spectrometry data show that SF3A1-UBL recognizes, sequence specifically, the GCG/CGC RNA stem and the apical UUCG tetraloop of U1-SL4. In vitro and in vivo mutational analyses support the observed intermolecular contacts and demonstrate that the carboxyl-terminal arginine-glycine-glycine-arginine (RGGR) motif of SF3A1-UBL binds sequence specifically by inserting into the RNA major groove. Thus, the characterization of the SF3A1-UBL/U1-SL4 complex expands the repertoire of RNA binding domains and reveals the capacity of RGG/RG motifs to bind RNA in a sequence-specific manner.

PubMed: 35101980
DOI: 10.1073/pnas.2114092119

Experimental method

SOLUTION NMR