Advanced Search

Submit Manuscript

Volume 31, No 10, Oct 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 10, October 2021: 1088-1105

ORIGINAL ARTICLES

A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid–liquid phase separation to promote oncogenic YAP signaling

Rui-Hua Li1,† , Tian Tian2,† , Qi-Wei Ge1,3,† , Xin-Yu He1 , Cheng-Yu Shi1 , Jun-Hong Li1 , Zhen Zhang1 , Fang-Zhou Liu1 , Ling-Jie Sang1 , Zuo-Zhen Yang1 , Ya-Zhuo Liu1 , Yan Xiong4 , Qingfeng Yan1 , Xu Li5 , Huai-Qiang Ju2 , Jian Liu6,7 , Liang-Jing Wang3 , Jian-Zhong Shao1 , Wenqi Wang8 , Tianhua Zhou3,9,10 , Aifu Lin1,10,11,12,*

1MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China
2Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
3Department of Gastroenterology, the Second Affiliated Hospital, School of Medicine and Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China
4Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
5Key Laboratory of Structural Biology of Zhejiang Province, Westlake Laboratory of Life Sciences and Biomedicine, Westlake University, Hangzhou, Zhejiang, China
6Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, Zhejiang, China
7Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
8Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA
9Department of Cell Biology and Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
10Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China.
11Breast Center of the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, Chin
12Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou, Zhejiang, China
†These authors contributed equally: Rui-Hua Li, Tian Tian, Qi-Wei Ge
Correspondence: Aifu Lin(linaifu@zju.edu.cn)

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid–liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).


https://doi.org/10.1038/s41422-021-00530-9

FULL TEXT | PDF

Browse 974