The structure and selectivity of the SR protein SRSF2 RRM domain with RNA.

Phelan, Marie M, Goult, Benjamin T ORCID: 0000-0002-3438-2807, Clayton, Jonathan C, Hautbergue, Guillaume M, Wilson, Stuart A ORCID: 0000-0003-3073-258X and Lian, Lu-Yun (2012) The structure and selectivity of the SR protein SRSF2 RRM domain with RNA. Nucleic acids research, 40 (7). pp. 3232-3244.

PDF
The structure and selectivity of the SR protein SRSF2 RRM domain with RNA.pdf - Open Access published version
Download (10MB) | Preview

Official URL: http://dx.doi.org/10.1093/nar/gkr1164

Abstract

SRSF2 is a prototypical SR protein which plays important roles in the alternative splicing of pre-mRNA. It has been shown to be involved in regulatory pathways for maintaining genomic stability and play important roles in regulating key receptors in the heart. We report here the solution structure of the RNA recognition motifs (RRM) domain of free human SRSF2 (residues 9-101). Compared with other members of the SR protein family, SRSF2 structure has a longer L3 loop region. The conserved aromatic residue in the RNP2 motif is absent in SRSF2. Calorimetric titration shows that the RNA sequence 5'AGCAGAGUA3' binds SRSF2 with a K(d) of 61 ± 1 nM and a 1:1 stoichiometry. NMR and mutagenesis experiments reveal that for SFSF2, the canonical β1 and β3 interactions are themselves not sufficient for effective RNA binding; the additional loop L3 is crucial for RNA complex formation. A comparison is made between the structures of SRSF2-RNA complex with other known RNA complexes of SR proteins. We conclude that interactions involving the L3 loop, N- and C-termini of the RRM domain are collectively important for determining selectivity between the protein and RNA.

Item Type:	Article
Additional Information:	## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords:	Humans, Ribonucleoproteins, Nuclear Proteins, RNA, Calorimetry, Nuclear Magnetic Resonance, Biomolecular, Mutagenesis, Binding Sites, Amino Acid Sequence, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Models, Molecular, Molecular Sequence Data, Serine-Arginine Splicing Factors
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 Mar 2024 09:35
Last Modified:	13 Mar 2024 09:35
DOI:	10.1093/nar/gkr1164
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179348