RRC ID 61883
Author Guo X, Sun Y, Azad T, Janse van Rensburg HJ, Luo J, Yang S, Liu P, Lv Z, Zhan M, Lu L, Zhou Y, Ma X, Zhang X, Yang X, Xue L.
Title Rox8 promotes microRNA-dependent yki messenger RNA decay.
Journal Proc Natl Acad Sci U S A
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.
Volume 117(48)
Pages 30520-30530
Published 2020-12-1
DOI 10.1073/pnas.2013449117
PII 2013449117
PMID 33203680
PMC PMC7720199
MeSH 3' Untranslated Regions Animals Cell Proliferation Drosophila Proteins / genetics* Drosophila melanogaster / genetics* Fluorescent Antibody Technique Gene Expression Regulation Hippo Signaling Pathway Humans MicroRNAs / genetics* Models, Biological Nuclear Proteins / genetics* Organ Specificity Protein Serine-Threonine Kinases / metabolism RNA Interference RNA Stability RNA, Messenger* RNA-Binding Proteins / genetics* Signal Transduction Trans-Activators / genetics* YAP-Signaling Proteins
IF 9.412
Drosophila 5422R-1 DGRC#200784