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

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 o...

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Main Authors:	Phelan, Marie M., Goult, Benjamin T., Clayton, Jonathan C., Hautbergue, Guillaume M., Wilson, Stuart A., Lian, Lu-Yun
Format:	Online
Language:	English
Published:	Oxford University Press 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326313/

id	pubmed-3326313
recordtype	oai_dc
spelling	pubmed-33263132012-04-16 The structure and selectivity of the SR protein SRSF2 RRM domain with RNA Phelan, Marie M. Goult, Benjamin T. Clayton, Jonathan C. Hautbergue, Guillaume M. Wilson, Stuart A. Lian, Lu-Yun Structural Biology 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 Kd 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. Oxford University Press 2012-04 2011-12-02 /pmc/articles/PMC3326313/ /pubmed/22140111 http://dx.doi.org/10.1093/nar/gkr1164 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Phelan, Marie M. Goult, Benjamin T. Clayton, Jonathan C. Hautbergue, Guillaume M. Wilson, Stuart A. Lian, Lu-Yun
spellingShingle	Phelan, Marie M. Goult, Benjamin T. Clayton, Jonathan C. Hautbergue, Guillaume M. Wilson, Stuart A. Lian, Lu-Yun The structure and selectivity of the SR protein SRSF2 RRM domain with RNA
author_facet	Phelan, Marie M. Goult, Benjamin T. Clayton, Jonathan C. Hautbergue, Guillaume M. Wilson, Stuart A. Lian, Lu-Yun
author_sort	Phelan, Marie M.
title	The structure and selectivity of the SR protein SRSF2 RRM domain with RNA
title_short	The structure and selectivity of the SR protein SRSF2 RRM domain with RNA
title_full	The structure and selectivity of the SR protein SRSF2 RRM domain with RNA
title_fullStr	The structure and selectivity of the SR protein SRSF2 RRM domain with RNA
title_full_unstemmed	The structure and selectivity of the SR protein SRSF2 RRM domain with RNA
title_sort	structure and selectivity of the sr protein srsf2 rrm domain with rna
description	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 Kd 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.
publisher	Oxford University Press
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326313/
_version_	1611520968474230784

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

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