Rox8 promotes microRNA-dependent yki messenger RNA decay.

Autor:	Guo X; Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China., Sun Y; Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China.; Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, Guangdong 51900, China., Azad T; Department of Pathology and Molecular Medicine, Queen's University, Kingston, K7L 3N6, ON, Canada., Janse van Rensburg HJ; Department of Pathology and Molecular Medicine, Queen's University, Kingston, K7L 3N6, ON, Canada., Luo J; Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China., Yang S; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China.; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang 310024, China., Liu P; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China.; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang 310024, China., Lv Z; Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China., Zhan M; Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, Guangdong 51900, China., Lu L; Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, Guangdong 51900, China., Zhou Y; Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China., Ma X; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China; lei.xue@tongji.edu.cn maxianjue@westlake.edu.cn zxpkxy@126.com yangx@queensu.ca.; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang 310024, China., Zhang X; Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China; lei.xue@tongji.edu.cn maxianjue@westlake.edu.cn zxpkxy@126.com yangx@queensu.ca., Yang X; Department of Pathology and Molecular Medicine, Queen's University, Kingston, K7L 3N6, ON, Canada; lei.xue@tongji.edu.cn maxianjue@westlake.edu.cn zxpkxy@126.com yangx@queensu.ca., Xue L; Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China; lei.xue@tongji.edu.cn maxianjue@westlake.edu.cn zxpkxy@126.com yangx@queensu.ca.; Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, Guangdong 51900, China.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Dec 01; Vol. 117 (48), pp. 30520-30530. Date of Electronic Publication: 2020 Nov 17.
DOI:	10.1073/pnas.2013449117
Abstrakt:	The Hippo pathway is an evolutionarily conserved regulator of organ growth and tumorigenesis. In Drosophila , oncogenic Ras V12 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 Ras V12 /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. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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