Loedige, Inga and Jakob, Leonhard and Treiber, Thomas and Ray, Debashish and Stotz, Mathias and Treiber, Nora and Hennig, Janosch and Cook, Kate B. and Morris, Quaid and Hughes, Timothy R. and Engelmann, Julia C. and Krahn, Michael P. and Meister, Gunter (2015) The Crystal Structure of the NHL Domain in Complex with RNA Reveals the Molecular Basis of Drosophila Brain-Tumor-Mediated Gene Regulation. CELL REPORTS, 13 (6). pp. 1206-1220. ISSN 2211-1247,
Full text not available from this repository. (Request a copy)Abstract
TRIM-NHL proteins are conserved among metazoans and control cell fate decisions in various stem cell linages. The Drosophila TRIM-NHL protein Brain tumor (Brat) directs differentiation of neuronal stem cells by suppressing self-renewal factors. Brat is an RNA-binding protein and functions as a translational repressor. However, it is unknown which RNAs Brat regulates and how RNA-binding specificity is achieved. Using RNA immunoprecipitation and RNAcompete, we identify Brat-bound mRNAs in Drosophila embryos and define consensus binding motifs for Brat as well as a number of additional TRIM-NHL proteins, indicating that TRIM-NHL proteins are conserved, sequence-specific RNA-binding proteins. We demonstrate that Brat-mediated repression and direct RNA-binding depend on the identified motif and show that binding of the localization factor Miranda to the Brat-NHL domain inhibits Brat activity. Finally, to unravel the sequence specificity of the NHL domain, we crystallize the BratNHL domain in complex with RNA and present a high-resolution protein-RNA structure of this fold.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEURAL STEM-CELLS; HUNCHBACK MESSENGER-RNA; SELF-RENEWAL; BINDING PROTEINS; PUMILIO; EXPRESSION; RECOGNITION; SUPPRESSOR; MICRORNAS; MODEL; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 May 2019 08:13 |
| Last Modified: | 06 May 2019 08:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4463 |
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