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In vivo studies on the role of the RNA-binding protein TIAR

Units : Molecular biology of the gene | ULB130

Description :

TIAR and its homolog, TIA-1, belong to the family of RNA-binding proteins containing RNA-Recognition Motifs (RRM). As many
RNA-binding proteins, TIAR and TIA-1 accumulate both in the nucleus and the cytoplasm. In the nucleus, they are involved in the
alternative splicing of several hnRNAs (Förch et al., 2000). In vitro studies revealed that both TIA-1 and TIAR bind AU-rich elements
(ARE) located in the 3' untranslated regions of several mRNAs, such that encoding Tumor Necrosis Factor-; (TNF),  Granulocyte
Macrophage Colony Stimulating Factor (GM-CSF) and cyclooxygenase-2 (COX-2) (Gueydan et al., 1999; Cok et al., 2003). Furthermore, in vivo
studies demonstrated that TIA-1 acts as a translational repressor of TNF and COX-2 mRNAs. Indeed, tia-1 gene knock out induces an
enhanced production of TNF and COX-2 in monocyte/macrophages, resulting from an increased association of the mRNAs to the
translational machinery (Piecyk et al., 2000; Dixon et al., 2003). Finally, both TIA-1 and TIAR co-localize with poly(A)+ RNA in
cytoplasmic granules induced by environmental stresses (Kedersha et al., 1999; 2001). The importance of TIAR in the post-transcriptional
regulation of ARE-containing mRNAs has not been established. Indeed, the knock out of tiar gene is partially lethal and induces
infertility (Beck et al., 1998), thereby precluding the loss-of-function approach to analyze TIAR function in vivo. Therefore, we
generated transgenic mice overexpressing TIAR. However, ubiquitous and constitutive expression of TIAR leads to embryonic lethality
(unpublished results).

List of persons in charge :

  • KRUYS Véronique

List of lessors :

  • F.R.S.-FNRS et Fonds associés (hors FRIA)

  • Région wallonne

  • Financement de base institutionnel