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Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA

Splicing factor proline- and glutamine-rich (SFPQ) also commonly known as polypyrimidine tract-binding protein-associated-splicing factor (PSF) and its binding partner non-POU domain-containing octamer-binding protein (NONO/p54nrb), are highly abundant, multifunctional nuclear proteins. However, the...

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Autores principales: Snijders, Ambrosius P., Hautbergue, Guillaume M., Bloom, Alex, Williamson, James C., Minshull, Thomas C., Phillips, Helen L., Mihaylov, Simeon R., Gjerde, Douglas T., Hornby, David P., Wilson, Stuart A., Hurd, Paul J., Dickman, Mark J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338332/
https://www.ncbi.nlm.nih.gov/pubmed/25605962
http://dx.doi.org/10.1261/rna.045138.114
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author Snijders, Ambrosius P.
Hautbergue, Guillaume M.
Bloom, Alex
Williamson, James C.
Minshull, Thomas C.
Phillips, Helen L.
Mihaylov, Simeon R.
Gjerde, Douglas T.
Hornby, David P.
Wilson, Stuart A.
Hurd, Paul J.
Dickman, Mark J.
author_facet Snijders, Ambrosius P.
Hautbergue, Guillaume M.
Bloom, Alex
Williamson, James C.
Minshull, Thomas C.
Phillips, Helen L.
Mihaylov, Simeon R.
Gjerde, Douglas T.
Hornby, David P.
Wilson, Stuart A.
Hurd, Paul J.
Dickman, Mark J.
author_sort Snijders, Ambrosius P.
collection PubMed
description Splicing factor proline- and glutamine-rich (SFPQ) also commonly known as polypyrimidine tract-binding protein-associated-splicing factor (PSF) and its binding partner non-POU domain-containing octamer-binding protein (NONO/p54nrb), are highly abundant, multifunctional nuclear proteins. However, the exact role of this complex is yet to be determined. Following purification of the endogeneous SFPQ/NONO complex, mass spectrometry analysis identified a wide range of interacting proteins, including those involved in RNA processing, RNA splicing, and transcriptional regulation, consistent with a multifunctional role for SFPQ/NONO. In addition, we have identified several sites of arginine methylation in SFPQ/PSF using mass spectrometry and found that several arginines in the N-terminal domain of SFPQ/PSF are asymmetrically dimethylated. Furthermore, we find that the protein arginine N-methyltransferase, PRMT1, catalyzes this methylation in vitro and that this is antagonized by citrullination of SFPQ. Arginine methylation and citrullination of SFPQ/PSF does not affect complex formation with NONO. However, arginine methylation was shown to increase the association with mRNA in mRNP complexes in mammalian cells. Finally we show that the biochemical properties of the endogenous complex from cell lysates are significantly influenced by the ionic strength during purification. At low ionic strength, the SFPQ/NONO complex forms large heterogeneous protein assemblies or aggregates, preventing the purification of the SFPQ/NONO complex. The ability of the SFPQ/NONO complex to form varying protein assemblies, in conjunction with the effect of post-translational modifications of SFPQ modulating mRNA binding, suggests key roles affecting mRNP dynamics within the cell.
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spelling pubmed-43383322015-03-01 Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA Snijders, Ambrosius P. Hautbergue, Guillaume M. Bloom, Alex Williamson, James C. Minshull, Thomas C. Phillips, Helen L. Mihaylov, Simeon R. Gjerde, Douglas T. Hornby, David P. Wilson, Stuart A. Hurd, Paul J. Dickman, Mark J. RNA Articles Splicing factor proline- and glutamine-rich (SFPQ) also commonly known as polypyrimidine tract-binding protein-associated-splicing factor (PSF) and its binding partner non-POU domain-containing octamer-binding protein (NONO/p54nrb), are highly abundant, multifunctional nuclear proteins. However, the exact role of this complex is yet to be determined. Following purification of the endogeneous SFPQ/NONO complex, mass spectrometry analysis identified a wide range of interacting proteins, including those involved in RNA processing, RNA splicing, and transcriptional regulation, consistent with a multifunctional role for SFPQ/NONO. In addition, we have identified several sites of arginine methylation in SFPQ/PSF using mass spectrometry and found that several arginines in the N-terminal domain of SFPQ/PSF are asymmetrically dimethylated. Furthermore, we find that the protein arginine N-methyltransferase, PRMT1, catalyzes this methylation in vitro and that this is antagonized by citrullination of SFPQ. Arginine methylation and citrullination of SFPQ/PSF does not affect complex formation with NONO. However, arginine methylation was shown to increase the association with mRNA in mRNP complexes in mammalian cells. Finally we show that the biochemical properties of the endogenous complex from cell lysates are significantly influenced by the ionic strength during purification. At low ionic strength, the SFPQ/NONO complex forms large heterogeneous protein assemblies or aggregates, preventing the purification of the SFPQ/NONO complex. The ability of the SFPQ/NONO complex to form varying protein assemblies, in conjunction with the effect of post-translational modifications of SFPQ modulating mRNA binding, suggests key roles affecting mRNP dynamics within the cell. Cold Spring Harbor Laboratory Press 2015-03 /pmc/articles/PMC4338332/ /pubmed/25605962 http://dx.doi.org/10.1261/rna.045138.114 Text en © 2015 Snijders et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Articles
Snijders, Ambrosius P.
Hautbergue, Guillaume M.
Bloom, Alex
Williamson, James C.
Minshull, Thomas C.
Phillips, Helen L.
Mihaylov, Simeon R.
Gjerde, Douglas T.
Hornby, David P.
Wilson, Stuart A.
Hurd, Paul J.
Dickman, Mark J.
Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA
title Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA
title_full Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA
title_fullStr Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA
title_full_unstemmed Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA
title_short Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA
title_sort arginine methylation and citrullination of splicing factor proline- and glutamine-rich (sfpq/psf) regulates its association with mrna
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338332/
https://www.ncbi.nlm.nih.gov/pubmed/25605962
http://dx.doi.org/10.1261/rna.045138.114
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