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Citation
Guo, X., Sun, Y., Azad, T., Janse van Rensburg, H.J., Luo, J., Yang, S., Liu, P., Lv, Z., Zhan, M., Lu, L., Zhou, Y., Ma, X., Zhang, X., Yang, X., Xue, L. (2020). Rox8 promotes microRNA-dependent yki messenger RNA decay.  Proc. Natl. Acad. Sci. U.S.A. 117(48): 30520--30530.
FlyBase ID
FBrf0247432
Publication Type
Research paper
Abstract

The Hippo pathway is an evolutionarily conserved regulator of organ growth and tumorigenesis. In Drosophila, oncogenic RasV12 cooperates with loss-of-cell polarity to promote Hippo pathway-dependent tumor growth. To identify additional factors that modulate this signaling, we performed a genetic screen utilizing the Drosophila RasV12 /lgl-/- in vivo tumor model and identified Rox8, a RNA-binding protein (RBP), as a positive regulator of the Hippo pathway. We found that Rox8 overexpression suppresses whereas Rox8 depletion potentiates Hippo-dependent tissue overgrowth, accompanied by altered Yki protein level and target gene expression. Mechanistically, Rox8 directly binds to a target site located in the yki 3' UTR, recruits and stabilizes the targeting of miR-8-loaded RISC, which accelerates the decay of yki messenger RNA (mRNA). Moreover, TIAR, the human ortholog of Rox8, is able to promote the degradation of yki mRNA when introduced into Drosophila and destabilizes YAP mRNA in human cells. Thus, our study provides in vivo evidence that the Hippo pathway is posttranscriptionally regulated by the collaborative action of RBP and microRNA (miRNA), which may provide an approach for modulating Hippo pathway-mediated tumorigenesis.

PubMed ID
PubMed Central ID
PMC7720199 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference
    Alleles (34)
    Gene Groups (1)
    Genes (17)
    Human Disease Models (2)
    Physical Interactions (2)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (5)
    Experimental Tools (4)
    Transgenic Constructs (21)