Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing
Rac1b is an alternatively spliced isoform of the small GTPase Rac1 that includes the 57-nucleotide exon 3b. Rac1b was originally identified through its over-expression in breast and colorectal cancer cells, and has subsequently been implicated as a key player in a number of different oncogenic signa...
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v113_n7_p2319_Pelisch http://hdl.handle.net/20.500.12110/paper_07302312_v113_n7_p2319_Pelisch |
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paper:paper_07302312_v113_n7_p2319_Pelisch2023-06-08T15:43:45Z Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing Pelisch, Federico Gastón Risso, Guillermo Javier Blaustein Kappelmacher, Matias Quadrana, Leandro Daniel Srebrow, Anabella alternative splicing hnrnp matrix metalloprotease Rac1 heterogeneous nuclear ribonucleoprotein heterogeneous nuclear ribonucleoprotein A1 messenger RNA Rac1 protein stromelysin unclassified drug animal cell article cell transformation controlled study exon human human tissue mouse nonhuman priority journal protein binding protein expression protein secretion proteomics RNA splicing signal transduction Alternative Splicing Animals Cell Line, Tumor Epithelial Cells Female Heterogeneous-Nuclear Ribonucleoprotein Group A-B Mammary Glands, Animal Mammary Neoplasms, Animal Matrix Metalloproteinase 3 Mice Neuropeptides Protein Isoforms Proteomics rac GTP-Binding Proteins RNA Precursors RNA Splicing RNA, Messenger Rac1b is an alternatively spliced isoform of the small GTPase Rac1 that includes the 57-nucleotide exon 3b. Rac1b was originally identified through its over-expression in breast and colorectal cancer cells, and has subsequently been implicated as a key player in a number of different oncogenic signaling pathways, including tumorigenic transformation of mammary epithelial cells exposed to matrix metalloproteinase-3 (MMP-3). Although many of the cellular consequences of Rac1b activity have been recently described, the molecular mechanism by which MMP-3 treatment leads to Rac1b induction has not been defined. Here we use proteomic methods to identify heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as a factor involved in Rac1 splicing regulation. We find that hnRNP A1 binds to Rac1 exon 3b in mouse mammary epithelial cells, repressing its inclusion into mature mRNA. We also find that exposure of cells to MMP-3 leads to release of hnRNP A1 from exon 3b and the consequent generation of Rac1b. Finally, we analyze normal breast tissue and breast cancer biopsies, and identify an inverse correlation between expression of hnRNP A1 and Rac1b, suggesting the existence of this regulatory axis in vivo. These results provide new insights on how extracellular signals regulate alternative splicing, contributing to cellular transformation and development of breast cancer. © 2012 Wiley Periodicals, Inc. Fil:Pelisch, F. 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: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:Srebrow, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v113_n7_p2319_Pelisch http://hdl.handle.net/20.500.12110/paper_07302312_v113_n7_p2319_Pelisch |
| 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 hnrnp matrix metalloprotease Rac1 heterogeneous nuclear ribonucleoprotein heterogeneous nuclear ribonucleoprotein A1 messenger RNA Rac1 protein stromelysin unclassified drug animal cell article cell transformation controlled study exon human human tissue mouse nonhuman priority journal protein binding protein expression protein secretion proteomics RNA splicing signal transduction Alternative Splicing Animals Cell Line, Tumor Epithelial Cells Female Heterogeneous-Nuclear Ribonucleoprotein Group A-B Mammary Glands, Animal Mammary Neoplasms, Animal Matrix Metalloproteinase 3 Mice Neuropeptides Protein Isoforms Proteomics rac GTP-Binding Proteins RNA Precursors RNA Splicing RNA, Messenger |
| spellingShingle |
alternative splicing hnrnp matrix metalloprotease Rac1 heterogeneous nuclear ribonucleoprotein heterogeneous nuclear ribonucleoprotein A1 messenger RNA Rac1 protein stromelysin unclassified drug animal cell article cell transformation controlled study exon human human tissue mouse nonhuman priority journal protein binding protein expression protein secretion proteomics RNA splicing signal transduction Alternative Splicing Animals Cell Line, Tumor Epithelial Cells Female Heterogeneous-Nuclear Ribonucleoprotein Group A-B Mammary Glands, Animal Mammary Neoplasms, Animal Matrix Metalloproteinase 3 Mice Neuropeptides Protein Isoforms Proteomics rac GTP-Binding Proteins RNA Precursors RNA Splicing RNA, Messenger Pelisch, Federico Gastón Risso, Guillermo Javier Blaustein Kappelmacher, Matias Quadrana, Leandro Daniel Srebrow, Anabella Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing |
| topic_facet |
alternative splicing hnrnp matrix metalloprotease Rac1 heterogeneous nuclear ribonucleoprotein heterogeneous nuclear ribonucleoprotein A1 messenger RNA Rac1 protein stromelysin unclassified drug animal cell article cell transformation controlled study exon human human tissue mouse nonhuman priority journal protein binding protein expression protein secretion proteomics RNA splicing signal transduction Alternative Splicing Animals Cell Line, Tumor Epithelial Cells Female Heterogeneous-Nuclear Ribonucleoprotein Group A-B Mammary Glands, Animal Mammary Neoplasms, Animal Matrix Metalloproteinase 3 Mice Neuropeptides Protein Isoforms Proteomics rac GTP-Binding Proteins RNA Precursors RNA Splicing RNA, Messenger |
| description |
Rac1b is an alternatively spliced isoform of the small GTPase Rac1 that includes the 57-nucleotide exon 3b. Rac1b was originally identified through its over-expression in breast and colorectal cancer cells, and has subsequently been implicated as a key player in a number of different oncogenic signaling pathways, including tumorigenic transformation of mammary epithelial cells exposed to matrix metalloproteinase-3 (MMP-3). Although many of the cellular consequences of Rac1b activity have been recently described, the molecular mechanism by which MMP-3 treatment leads to Rac1b induction has not been defined. Here we use proteomic methods to identify heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as a factor involved in Rac1 splicing regulation. We find that hnRNP A1 binds to Rac1 exon 3b in mouse mammary epithelial cells, repressing its inclusion into mature mRNA. We also find that exposure of cells to MMP-3 leads to release of hnRNP A1 from exon 3b and the consequent generation of Rac1b. Finally, we analyze normal breast tissue and breast cancer biopsies, and identify an inverse correlation between expression of hnRNP A1 and Rac1b, suggesting the existence of this regulatory axis in vivo. These results provide new insights on how extracellular signals regulate alternative splicing, contributing to cellular transformation and development of breast cancer. © 2012 Wiley Periodicals, Inc. |
| author |
Pelisch, Federico Gastón Risso, Guillermo Javier Blaustein Kappelmacher, Matias Quadrana, Leandro Daniel Srebrow, Anabella |
| author_facet |
Pelisch, Federico Gastón Risso, Guillermo Javier Blaustein Kappelmacher, Matias Quadrana, Leandro Daniel Srebrow, Anabella |
| author_sort |
Pelisch, Federico Gastón |
| title |
Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing |
| title_short |
Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing |
| title_full |
Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing |
| title_fullStr |
Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing |
| title_full_unstemmed |
Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing |
| title_sort |
involvement of hnrnp a1 in the matrix metalloprotease-3-dependent regulation of rac1 pre-mrna splicing |
| publishDate |
2012 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v113_n7_p2319_Pelisch http://hdl.handle.net/20.500.12110/paper_07302312_v113_n7_p2319_Pelisch |
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| _version_ |
1768544554197188608 |