SNORD80-guided 2’-O-methylation stabilizes the lncRNA GAS5 to regulate cellular stress responses
Abstract
The introns of the gene encoding the long noncoding RNA (lncRNA) GAS5 host up to 10 C/D box small nucleolar RNAs (snoRNAs). However, whether there is a regulatory and functional relationship between these snoRNAs and GAS5 is unknown. Here, we show that the expression of SNORD80, but not the other snoRNAs, parallels GAS5 expression and is regulated alongside GAS5 in response to cellular stress. The 2′-O-methylation at the A496 site, located within a segment of GAS5 complementing the conserved RNA-binding region on SNORD80, promotes GAS5 stability and consequent upregulation. This methylation requires SNORD80, as it is diminished by knockdown of SNORD80 and increased by SNORD80 overexpression, similar to the effects of manipulating the expression of fibrillarin, the methyltransferase of the box C/D small nucleolar ribonucleoprotein particle (snoRNP). The upregulation of SNORD80 in response to cellular stress is due to an enhancement in its stability, which is associated with an increase in its interaction with fibrillarin. Collectively, these results identify a role for SNORD80 in guiding 2′-O-methylation to stabilize GAS5. This uncovers a feedforward regulatory loop at the GAS5 gene locus in response to cellular stress and sheds light on posttranscriptional mechanisms governing lncRNA expression.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (21)
Liang Xu
Xiao Hong Zhao
School of Biomedical Sciences and Pharmacy, The University of Newcastle
Yuan Yuan Zhang
School of Biomedical Sciences and Pharmacy, The University of Newcastle
Meng Yao Zhang
Translational Research Institute, Henan Provincial and Zhengzhou City Key laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People’s Hospital, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University
Long Yue Zhang
Translational Research Institute, Henan Provincial and Zhengzhou City Key laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People’s Hospital, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University
Kai Hong Ye
Translational Research Institute, Henan Provincial and Zhengzhou City Key laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People’s Hospital, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University
Liu Teng
Translational Research Institute, Henan Provincial and Zhengzhou City Key laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People’s Hospital, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University
Man Man Han
Translational Research Institute, Henan Provincial and Zhengzhou City Key laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People’s Hospital, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University
Yi Meng Yue
Translational Research Institute, Henan Provincial and Zhengzhou City Key laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People’s Hospital, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University
Jiezhen Yang
Department of Pathology, Zhongshan Hospital (Xiamen Branch), Fudan University
Rachel Ogle
School of Biomedical Sciences and Pharmacy, The University of Newcastle
Jacob Netherton
School of Biomedical Sciences and Pharmacy, The University of Newcastle
Deng Tang
West China School of Basic Medical Science and Forensic Medicine, Sichuan University
Siqi Lan
West China School of Basic Medical Science and Forensic Medicine, Sichuan University
Mark Baker
School of Biomedical Sciences and Pharmacy, The University of Newcastle
Yan Ye
State Key Laboratory of Chemistry for NBC Hazards Protection, College of Chemistry
Tao Liu
Yu Fang Wang
West China School of Basic Medical Science and Forensic Medicine, Sichuan University
Xu Dong Zhang
School of Biomedical Sciences and Pharmacy, The University of Newcastle
Tianli Fan
Department of Pharmacology, School of Basic Medicine, Zhengzhou University
Lei Jin