Ischemia induces a translocation of the splicing factor tra2-β1 and changes alternative splicing patterns in the brain

Rosette Daoud, Günter Mies, Agata Smialowska, L. Oláh, Konstantin Alexander Hossmann, Stefan Stamm

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

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 the ICH-1 gene. 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.

Original languageEnglish
Pages (from-to)5889-5899
Number of pages11
JournalJournal of Neuroscience
Volume22
Issue number14
Publication statusPublished - Jul 15 2002

Fingerprint

Alternative Splicing
Ischemia
Serine
Brain
Arginine
RNA Splice Sites
Proteins
Cytosol
Protein Splicing
Heterogeneous-Nuclear Ribonucleoproteins
Physiological Phenomena
Calcium
Thapsigargin
RNA Precursors
Mitosis
Protein Binding
Exons
RNA Splicing Factors
Genes

Keywords

  • Alternative pre-mRNA processing
  • Calcium
  • Ischemia
  • Phosphorylation
  • SR proteins
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ischemia induces a translocation of the splicing factor tra2-β1 and changes alternative splicing patterns in the brain. / Daoud, Rosette; Mies, Günter; Smialowska, Agata; Oláh, L.; Hossmann, Konstantin Alexander; Stamm, Stefan.

In: Journal of Neuroscience, Vol. 22, No. 14, 15.07.2002, p. 5889-5899.

Research output: Contribution to journalArticle

Daoud, Rosette ; Mies, Günter ; Smialowska, Agata ; Oláh, L. ; Hossmann, Konstantin Alexander ; Stamm, Stefan. / Ischemia induces a translocation of the splicing factor tra2-β1 and changes alternative splicing patterns in the brain. In: Journal of Neuroscience. 2002 ; Vol. 22, No. 14. pp. 5889-5899.
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