7P0V

Crystal structure of human SF3A1 ubiquitin-like domain in complex with U1 snRNA stem-loop 4

Summary for 7P0V

• Entry DOI: 10.2210/pdb7p0v/pdb
• Related: 7P08
• Descriptor: Isoform 2 of Splicing factor 3A subunit 1, RNA (5'-R(P*GP*GP*GP*GP*AP*CP*UP*GP*CP*GP*UP*UP*CP*GP*CP*GP*CP*UP*UP*UP*CP*CP*CP*C)-3'), PENTAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: splicing, rgg/rg motif, intrinsically disordered region, rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 18129.72

Authors

Sabath, K.,de Vries, T.,Jonas, S. (deposition date: 2021-06-30, release date: 2022-04-20, Last modification date: 2024-01-31)

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

X-RAY DIFFRACTION (1.56 Å)