Ischemia induces a translocation of the splicing factor tra2-beta 1 and changes alternative splicing patterns in the brain
| Autor: | Stefan Stamm, Konstantin Alexander Hossmann, Agata Smialowska, Günter Mies, Rosette Daoud, László Oláh |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Calcium-Transporting ATPases Biology Heterogeneous ribonucleoprotein particle Brain Ischemia Sarcoplasmic Reticulum Calcium-Transporting ATPases Exon Splicing factor Mice SR protein Cytosol Protein splicing RNA Precursors Animals Drosophila Proteins Protein Isoforms Enzyme Inhibitors Phosphorylation ARTICLE Cells Cultured Cell Nucleus Neurons General Neuroscience Alternative splicing Caspase 2 Brain Nuclear Proteins RNA-Binding Proteins Cell biology Rats Mice Inbred C57BL Alternative Splicing Disease Models Animal Protein Transport Biochemistry Ribonucleoproteins Caspases RNA splicing Calcium |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 22(14) |
| ISSN: | 1529-2401 |
| Popis: | Alternative splice-site selection is regulated by the relative concentration of individual members of the serine-arginine family of proteins and heterogeneous nuclear ribonucleoproteins. Most of these proteins accumulate predominantly in the nucleus, and a subset of them shuttles continuously between nucleus and cytosol. We demonstrate that in primary neuronal cultures, a rise in intracellular calcium concentration induced by thapsigargin leads to a translocation of the splicing regulatory protein tra2-β1 and a consequent change in splice-site selection. To investigate this phenomenon under physiological conditions, we used an ischemia model. Ischemia induced in the brain causes a cytoplasmic accumulation and hyperphosphorylation of tra2-β1. In addition, several of the proteins binding to tra2-β1, such as src associated in mitosis 68 and serine/arginine-rich proteins, accumulate in the cytosol. Concomitant with this subcellular relocalization, we observed a change in alternative splice-site usage of theICH-1gene. The increased usage of its alternative exons is in agreement with previous studies demonstrating its repression by a high concentration of proteins with serine/arginine-rich domains. Our findings suggest that a change in the calcium concentration associated with ischemia is part of a signaling event, which changes pre-mRNA splicing pathways by causing relocalization of proteins that regulate splice-site selection. |
| Databáze: | OpenAIRE |
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