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Citation
Komori, H., Golden, K.L., Kobayashi, T., Kageyama, R., Lee, C.Y. (2018). Multilayered gene control drives timely exit from the stem cell state in uncommitted progenitors during Drosophila asymmetric neural stem cell division.  Genes Dev. 32(23-24): 1550--1561.
FlyBase ID
FBrf0240730
Publication Type
Research paper
Abstract

Self-renewal genes maintain stem cells in an undifferentiated state by preventing the commitment to differentiate. Robust inactivation of self-renewal gene activity following asymmetric stem cell division allows uncommitted stem cell progeny to exit from an undifferentiated state and initiate the commitment to differentiate. Nonetheless, how self-renewal gene activity at mRNA and protein levels becomes synchronously terminated in uncommitted stem cell progeny is unclear. We demonstrate that a multilayered gene regulation system terminates self-renewal gene activity at all levels in uncommitted stem cell progeny in the fly neural stem cell lineage. We found that the RNA-binding protein Brain tumor (Brat) targets the transcripts of a self-renewal gene, deadpan (dpn), for decay by recruiting the deadenylation machinery to the 3' untranslated region (UTR). Furthermore, we identified a nuclear protein, Insensible, that complements Cullin-mediated proteolysis to robustly inactivate Dpn activity by limiting the level of active Dpn through protein sequestration. The synergy between post-transcriptional and transcriptional control of self-renewal genes drives timely exit from the stem cell state in uncommitted progenitors. Our proposed multilayered gene regulation system could be broadly applicable to the control of exit from stemness in all stem cell lineages.

PubMed ID
PubMed Central ID
PMC6295162 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genes Dev.
    Title
    Genes & Development
    Publication Year
    1987-
    ISBN/ISSN
    0890-9369
    Data From Reference
    Aberrations (27)
    Alleles (39)
    Genes (18)
    Physical Interactions (8)
    Cell Lines (1)
    Natural transposons (2)
    Insertions (2)
    Experimental Tools (7)
    Transgenic Constructs (24)