Rox8 promotes microRNA-dependent yki messenger RNA decay.

Proceedings of the National Academy of Sciences of the United States of America
Xiaowei GuoLei Xue

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 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.

References

Sep 23, 2003·Nature Cell Biology·Ryan S UdanGeorg Halder
Sep 23, 2003·Nature Cell Biology·Sophie PantalacciPierre Léopold
Oct 11, 2003·Science·Raymond A Pagliarini, Tian Xu
Sep 19, 2006·Nature Genetics·Eunjoo ChoKenneth D Irvine
Apr 18, 2007·Genes & Development·Duojia Pan
Jun 27, 2008·Genes & Development·Bin ZhaoKun-Liang Guan
Oct 29, 2008·Current Opinion in Cell Biology·Bin ZhaoKun-Liang Guan
Jan 24, 2009·Fly·Lei ZhangJin Jiang
May 5, 2010·Genes & Development·Bin ZhaoKun-Liang Guan
Oct 19, 2010·Developmental Cell·Duojia Pan
Dec 9, 2010·Development·Georg Halder, Randy L Johnson
Nov 1, 2011·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Mengxin Yin, Lei Zhang
Nov 10, 2011·Development·B V V G Reddy, Kenneth D Irvine
Jul 31, 2012·Current Biology : CB·Carole L C PoonKieran F Harvey
Jul 31, 2012·Current Biology : CB·Joanna Chen, Esther M Verheyen
Mar 8, 2013·Nature Reviews. Cancer·Kieran F HarveyDavid M Thomas
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Jan 15, 2014·Genome Biology·Bobak Kechavarzi, Sarath Chandra Janga
Apr 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Paulo RibeiroNicolas Tapon
Dec 2, 2014·Nature Cell Biology·Biao MaShian Wu
Feb 10, 2016·Trends in Cancer·Meagan B RyanAdrienne D Cox
Mar 10, 2016·Developmental Cell·Hyung-Lok ChungKwang-Wook Choi
Jun 15, 2016·Cancer Cell·Francesca ZanconatoStefano Piccolo
Nov 20, 2016·Biochemical and Biophysical Research Communications·Liangchang HuShian Wu
Feb 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Xianjue MaLei Xue
Jul 19, 2017·Trends in Cancer·Bruno PereiraRaquel Almeida

❮ Previous
Next ❯

Citations

Jan 16, 2021·International Journal of Molecular Sciences·Wing-Keung ChuJan-Kan Chen
Aug 6, 2021·Cell Death Discovery·Chenxi WuLei Xue
Nov 3, 2021·Wiley Interdisciplinary Reviews. RNA·Pierre-Marc Frédérick, Martin J Simard

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.