SNAP output for PDB entry 7p0v [SNAP web server]

PDB-id

7p0v; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein

Method

X-ray (1.56 Å)

Summary

Crystal structure of human sf3a1 ubiquitin-like domain in complex with u1 snrna stem-loop 4

Reference

de Vries T, Martelly W, Campagne S, Sabath K, Sarnowski CP, Wong J, Leitner A, Jonas S, Sharma S, Allain FH (2022): "Sequence-specific RNA recognition by an RGG motif connects U1 and U2 snRNP for spliceosome assembly." Proc.Natl.Acad.Sci.USA, 119. doi: 10.1073/pnas.2114092119.

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.