Rapid Proteasomal Degradation of Posttranscriptional Regulators of the TIS11/Tristetraprolin Family Is Induced by an Intrinsically Unstructured Region Independently of Ubiquitination
| Autor: | Long Vo Ngoc, Romuald Soin, Sabrina Bousbata, Corinne Wauquier, Laure Twyffels, Véronique Kruys, Cyril Gueydan |
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| Rok vydání: | 2014 |
| Předmět: |
Proteasome Endopeptidase Complex
RNA Stability Tristetraprolin RNA-binding protein Intrinsically disordered proteins Cell Line Mice Ubiquitin Animals Drosophila Proteins Humans RNA Processing Post-Transcriptional RNA Small Interfering 3' Untranslated Regions Molecular Biology AU Rich Elements Zinc finger AU-rich element biology Three prime untranslated region Ubiquitination RNA-Binding Proteins Articles Cell Biology Molecular biology Cell biology Intrinsically Disordered Proteins Drosophila melanogaster HEK293 Cells Gene Expression Regulation Proteasome biology.protein RNA Interference |
| Zdroj: | Molecular and Cellular Biology. 34:4315-4328 |
| ISSN: | 1098-5549 |
| Popis: | The TIS11/tristetraprolin (TTP) CCCH tandem zinc finger proteins are major effectors in the destabilization of mRNAs bearing AU-rich elements (ARE) in their 3′ untranslated regions. In this report, we demonstrate that the Drosophila melanogaster dTIS11 protein is short-lived due to its rapid ubiquitin-independent degradation by the proteasome. Our data indicate that this mechanism is tightly associated with the intrinsically unstructured, disordered N- and C-terminal domains of the protein. Furthermore, we show that TTP, the mammalian TIS11/TTP protein prototype, shares the same three-dimensional characteristics and is degraded by the same proteolytic pathway as dTIS11, thereby indicating that this mechanism has been conserved across evolution. Finally, we observed a phosphorylation-dependent inhibition of dTIS11 and TTP degradation by the proteasome in vitro, raising the possibility that such modifications directly affect proteasomal recognition for these proteins. As a group, RNA-binding proteins (RNA-BPs) have been described as enriched in intrinsically disordered regions, thus raising the possibility that the mechanism that we uncovered for TIS11/TTP turnover is widespread among other RNA-BPs. |
| Databáze: | OpenAIRE |
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