Reichardt, Ilka and Bonnay, Francois and Steinmann, Victoria and Loedige, Inga and Burkard, Thomas R. and Meister, Gunter and Knoblich, Juergen A. (2018) The tumor suppressor Brat controls neuronal stem cell lineages by inhibiting Deadpan and Zelda. EMBO REPORTS, 19 (1). pp. 102-117. ISSN 1469-221X, 1469-3178
Full text not available from this repository. (Request a copy)Abstract
The TRIM-NHL protein Brain tumor (Brat) acts as a tumor suppressor in the Drosophila brain, but how it suppresses tumor formation is not completely understood. Here, we combine temperaturecontrolled brat RNAi with transcriptome analysis to identify the immediate Brat targets in Drosophila neuroblasts. Besides the known target Deadpan (Dpn), our experiments identify the transcription factor Zelda (Zld) as a critical target of Brat. Our data show that Zld is expressed in neuroblasts and required to allow re-expression of Dpn in transit-amplifying intermediate neural progenitors. Upon neuroblast division, Brat is enriched in one daughter cell where its NHL domain directly binds to specific motifs in the 3'UTR of dpn and zld mRNA to mediate their degradation. In brat mutants, both Dpn and Zld continue to be expressed, but inhibition of either transcription factor prevents tumorigenesis. Our genetic and biochemical data indicate that Dpn inhibition requires higher Brat levels than Zld inhibition and suggest a model where stepwise post-transcriptional inhibition of distinct factors ensures sequential generation of fates in a stem cell lineage.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RNA-BINDING PROTEIN; MESSENGER-RNA; SELF-RENEWAL; DROSOPHILA-MELANOGASTER; ASYMMETRIC SEGREGATION; PROGENITOR CELLS; NEUROBLAST LINEAGES; FACS PURIFICATION; HUMAN NEOCORTEX; NHL DOMAIN; neurogenesis; stem cells; tumorigenesis; RNA-binding protein |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2020 14:00 |
| Last Modified: | 23 Mar 2020 14:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15471 |
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