SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms

Post-splicing activities have been described for a subset of shuttling serine/arginine-rich splicing regulatory proteins, among them SF2/ASF. We showed that growth factors activate a Ras-PI 3-kinase-Akt/PKB signaling pathway that not only modifies alternative splicing of the fibronectin EDA exon, bu...

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Autores principales:	Blaustein Kappelmacher, Matias, Quadrana, Leandro Daniel, Risso, Guillermo Javier, de la Mata, Manuel, Pelisch, Federico Gastón, Srebrow, Anabella
Publicado:	2009
Materias:	Alternative splicing Cap-dependent translation FGF-2 IRES-dependent translation SF2/ASF SR proteins arginine ectodysplasin A fibroblast growth factor 2 fibronectin messenger RNA phosphatidylinositol 3 kinase protein asf protein kinase B protein sf2 Ras protein serine unclassified drug article human human cell in vivo study internal ribosome entry site priority journal protein expression protein function protein motif proteomics translation initiation Eukaryota
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v107_n4_p826_Blaustein http://hdl.handle.net/20.500.12110/paper_07302312_v107_n4_p826_Blaustein
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_07302312_v107_n4_p826_Blaustein
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spelling	paper:paper_07302312_v107_n4_p826_Blaustein2023-06-08T15:43:43Z SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms Blaustein Kappelmacher, Matias Quadrana, Leandro Daniel Risso, Guillermo Javier de la Mata, Manuel Pelisch, Federico Gastón Srebrow, Anabella Alternative splicing Cap-dependent translation FGF-2 IRES-dependent translation SF2/ASF SR proteins arginine ectodysplasin A fibroblast growth factor 2 fibronectin messenger RNA phosphatidylinositol 3 kinase protein asf protein kinase B protein sf2 Ras protein serine unclassified drug article human human cell in vivo study internal ribosome entry site priority journal protein expression protein function protein motif proteomics translation initiation Eukaryota Post-splicing activities have been described for a subset of shuttling serine/arginine-rich splicing regulatory proteins, among them SF2/ASF. We showed that growth factors activate a Ras-PI 3-kinase-Akt/PKB signaling pathway that not only modifies alternative splicing of the fibronectin EDA exon, but also alters in vivo translation of reporter mRNAs containing the EDA binding motif for SF2/ASF, providing two co-regulated levels of isoform-specific amplification. Translation of most eukaryotic mRNAs is initiated via the scanning mechanism, which implicates recognition of the m7G cap at the mRNA 50-terminus by the eIF4F protein complex. Several viral and cellular mRNAs are translated in a cap-independent manner by the action of cis-acting mRNA elements named internal ribosome entry sites that direct internal ribosome binding to the mRNA. Here we use bicistronic reporters that generate mRNAs carrying two open reading frames, one translated in a cap-dependent manner while the other by internal ribosome entry site-dependent initiation, to show that in vivo over-expression of SF2/ASF increases the ratio between cap-dependent and internal ribosome entry site-dependent translation. Consistently, knocking-down of SF2/ASF causes the opposite effect. Changes in expression levels of SF2/ASF also affect alternative translation of an endogenous mRNA, that one coding for fibroblast growth factor-2. These results strongly suggest a role for SF2/ASF as a regulator of alternative translation, meaning the generation of different proteins by the balance among these two translation initiation mechanisms, and expand the known potential of SF2/ASF to regulate proteomic diversity to the translation field. © 2009 Wiley-Liss, Inc. Fil:Blaustein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Quadrana, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Risso, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:De La Mata, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pelisch, F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Srebrow, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v107_n4_p826_Blaustein http://hdl.handle.net/20.500.12110/paper_07302312_v107_n4_p826_Blaustein
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Alternative splicing Cap-dependent translation FGF-2 IRES-dependent translation SF2/ASF SR proteins arginine ectodysplasin A fibroblast growth factor 2 fibronectin messenger RNA phosphatidylinositol 3 kinase protein asf protein kinase B protein sf2 Ras protein serine unclassified drug article human human cell in vivo study internal ribosome entry site priority journal protein expression protein function protein motif proteomics translation initiation Eukaryota
spellingShingle	Alternative splicing Cap-dependent translation FGF-2 IRES-dependent translation SF2/ASF SR proteins arginine ectodysplasin A fibroblast growth factor 2 fibronectin messenger RNA phosphatidylinositol 3 kinase protein asf protein kinase B protein sf2 Ras protein serine unclassified drug article human human cell in vivo study internal ribosome entry site priority journal protein expression protein function protein motif proteomics translation initiation Eukaryota Blaustein Kappelmacher, Matias Quadrana, Leandro Daniel Risso, Guillermo Javier de la Mata, Manuel Pelisch, Federico Gastón Srebrow, Anabella SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms
topic_facet	Alternative splicing Cap-dependent translation FGF-2 IRES-dependent translation SF2/ASF SR proteins arginine ectodysplasin A fibroblast growth factor 2 fibronectin messenger RNA phosphatidylinositol 3 kinase protein asf protein kinase B protein sf2 Ras protein serine unclassified drug article human human cell in vivo study internal ribosome entry site priority journal protein expression protein function protein motif proteomics translation initiation Eukaryota
description	Post-splicing activities have been described for a subset of shuttling serine/arginine-rich splicing regulatory proteins, among them SF2/ASF. We showed that growth factors activate a Ras-PI 3-kinase-Akt/PKB signaling pathway that not only modifies alternative splicing of the fibronectin EDA exon, but also alters in vivo translation of reporter mRNAs containing the EDA binding motif for SF2/ASF, providing two co-regulated levels of isoform-specific amplification. Translation of most eukaryotic mRNAs is initiated via the scanning mechanism, which implicates recognition of the m7G cap at the mRNA 50-terminus by the eIF4F protein complex. Several viral and cellular mRNAs are translated in a cap-independent manner by the action of cis-acting mRNA elements named internal ribosome entry sites that direct internal ribosome binding to the mRNA. Here we use bicistronic reporters that generate mRNAs carrying two open reading frames, one translated in a cap-dependent manner while the other by internal ribosome entry site-dependent initiation, to show that in vivo over-expression of SF2/ASF increases the ratio between cap-dependent and internal ribosome entry site-dependent translation. Consistently, knocking-down of SF2/ASF causes the opposite effect. Changes in expression levels of SF2/ASF also affect alternative translation of an endogenous mRNA, that one coding for fibroblast growth factor-2. These results strongly suggest a role for SF2/ASF as a regulator of alternative translation, meaning the generation of different proteins by the balance among these two translation initiation mechanisms, and expand the known potential of SF2/ASF to regulate proteomic diversity to the translation field. © 2009 Wiley-Liss, Inc.
author	Blaustein Kappelmacher, Matias Quadrana, Leandro Daniel Risso, Guillermo Javier de la Mata, Manuel Pelisch, Federico Gastón Srebrow, Anabella
author_facet	Blaustein Kappelmacher, Matias Quadrana, Leandro Daniel Risso, Guillermo Javier de la Mata, Manuel Pelisch, Federico Gastón Srebrow, Anabella
author_sort	Blaustein Kappelmacher, Matias
title	SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms
title_short	SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms
title_full	SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms
title_fullStr	SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms
title_full_unstemmed	SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms
title_sort	sf2/asf regulates proteomic diversity by affecting the balance between translation initiation mechanisms
publishDate	2009
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v107_n4_p826_Blaustein http://hdl.handle.net/20.500.12110/paper_07302312_v107_n4_p826_Blaustein
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_version_	1768541942213246976

SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms

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