Title |
Rapid Proteasomal Degradation of Posttranscriptional Regulators of the TIS11/Tristetraprolin Family Is Induced by an Intrinsically Unstructured Region Independently of Ubiquitination
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Published in |
Molecular & Cellular Biology, March 2023
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DOI | 10.1128/mcb.00643-14 |
Pubmed ID | |
Authors |
Long Vo Ngoc, Corinne Wauquier, Romuald Soin, Sabrina Bousbata, Laure Twyffels, Véronique Kruys, Cyril Gueydan |
Abstract |
The TTP/TIS11 CCCH tandem zinc finger proteins are major effectors in the destabilization of mRNAs bearing AU-rich elements (ARE) in their 3' untranslated region. In this report, we demonstrate that the Drosophila dTIS11 protein is short-lived due to its rapid ubiquitin-independent degradation by the proteasome. Our data indicate that this mechanism is tightly associated to the intrinsically disordered N- and C- terminal domains of the protein. Furthermore, we show that Tristetraprolin (TTP), the mammalian TTP/TIS11 protein prototype, shares the same three-dimensional characteristics and is degraded by the same proteolytic pathway as dTIS11, thereby indicating that this mechanism is 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 could directly affect proteasomal recognition for these proteins. As a group, RNA-binding proteins (RNA-BP) have been described as enriched in intrinsically disordered regions, thus raising the possibility that the mechanism we uncovered for TTP/TIS11 turnover may be widespread among other RNA-BPs. |
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