TP53-inducible putative long noncoding RNAs encode functional polypeptides that suppress cell proliferation
- Wenli Xu1,
- Chang Liu2,
- Bing Deng2,
- Penghui Lin2,
- Zhenghua Sun3,
- Anrui Liu2,
- Jiajia Xuan2,
- Yuying Li3,
- Keren Zhou2,
- Xiaoqin Zhang4,
- Qiaojuan Huang2,
- Hui Zhou2,
- Qingyu He3,
- Bin Li2,
- Lianghu Qu2 and
- Jianhua Yang5,6
- 1 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, The Third Affiliated Hospital, Sun Yat-sen University;
- 2 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, Sun Yat-sen University;
- 3 Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University;
- 4 South China University of Technology;
- 5 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol,The Fifth Affiliated Hospital, Sun Yat-sen University
Abstract
Polypeptides encoded by long non-coding RNAs (lncRNAs) are a novel class of functional molecules. However, whether these hidden polypeptides participate in the TP53 pathway and play a significant biological role is still unclear. Here, we discover that TP53-regulated lncRNAs encode peptides, two of which are functional in various human cell lines. Using ribosome profiling and RNA-seq approaches in HepG2 cells, we systematically identified more than 300 novel TP53-regulated lncRNAs and further confirmed that fifteen of these TP53-regulated lncRNAs encode peptides. Furthermore, several peptides were validated by multiple mass spectrometry measures. Ten of the novel translational lncRNAs were directly inducible by TP53 in response to DNA damage. Notably, we showed that the TP53-inducible peptides TP53LC02 and TP53LC04, but not their lncRNAs, could suppress cell proliferation. TP53LC04 peptide also had a function associated with cell proliferation by regulating the cell cycle in response to DNA damage. This study demonstrates that TP53-inducible lncRNAs encode new functional peptides, leading to the enlargement of the components of TP53 tumor suppressor network and providing novel potential targets for cancer therapy.
- Received June 3, 2021.
- Accepted May 6, 2022.
- Published by Cold Spring Harbor Laboratory Press
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