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Abstract:

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.

Registro:

Documento: Artículo
Título:SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms
Autor:Blaustein, M.; Quadrana, L.; Risso, G.; De La Mata, M.; Pelisch, F.; Srebrow, A.
Filiación:Laboratorio de Fisiología Y Biología Molecular, Instituto de Fisiología, Biología Molecular Y Neurociencias, Consejo Nacional de Investigaciones Científicas Y Técnicas, Buenos Aires, Argentina
Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Pabellón 2, (C1428EHA), Buenos Aires, Argentina
Palabras clave: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
Año:2009
Volumen:107
Número:4
Página de inicio:826
Página de fin:833
DOI: http://dx.doi.org/10.1002/jcb.22181
Título revista:Journal of Cellular Biochemistry
Título revista abreviado:J. Cell. Biochem.
ISSN:07302312
CODEN:JCEBD
CAS:arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; fibroblast growth factor 2, 106096-93-9; fibronectin, 86088-83-7; phosphatidylinositol 3 kinase, 115926-52-8; protein kinase B, 148640-14-6; serine, 56-45-1, 6898-95-9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v107_n4_p826_Blaustein

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Citas:

---------- APA ----------
Blaustein, M., Quadrana, L., Risso, G., De La Mata, M., Pelisch, F. & Srebrow, A. (2009) . SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms. Journal of Cellular Biochemistry, 107(4), 826-833.
http://dx.doi.org/10.1002/jcb.22181
---------- CHICAGO ----------
Blaustein, M., Quadrana, L., Risso, G., De La Mata, M., Pelisch, F., Srebrow, A. "SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms" . Journal of Cellular Biochemistry 107, no. 4 (2009) : 826-833.
http://dx.doi.org/10.1002/jcb.22181
---------- MLA ----------
Blaustein, M., Quadrana, L., Risso, G., De La Mata, M., Pelisch, F., Srebrow, A. "SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms" . Journal of Cellular Biochemistry, vol. 107, no. 4, 2009, pp. 826-833.
http://dx.doi.org/10.1002/jcb.22181
---------- VANCOUVER ----------
Blaustein, M., Quadrana, L., Risso, G., De La Mata, M., Pelisch, F., Srebrow, A. SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms. J. Cell. Biochem. 2009;107(4):826-833.
http://dx.doi.org/10.1002/jcb.22181