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Citation
Reichardt, I., Bonnay, F., Steinmann, V., Loedige, I., Burkard, T.R., Meister, G., Knoblich, J.A. (2018). The tumor suppressor Brat controls neuronal stem cell lineages by inhibiting Deadpan and Zelda.  EMBO Rep. 19(1): 102--117.
FlyBase ID
FBrf0237716
Publication Type
Research paper
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 temperature-controlled 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.
PubMed ID
PubMed Central ID
PMC5757284 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    EMBO Rep.
    Title
    EMBO Reports
    Publication Year
    2000-
    ISBN/ISSN
    1469-221X 1469-3178
    Data From Reference
    Alleles (39)
    Genes (9)
    Physical Interactions (3)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (5)
    Transgenic Constructs (33)