RT Journal
A1 Xu, Wenli
A1 Liu, Chang
A1 Deng, Bing
A1 Lin, Penghui
A1 Sun, Zhenghua
A1 Liu, Anrui
A1 Xuan, Jiajia
A1 Li, Yuying
A1 Zhou, Keren
A1 Zhang, Xiaoqin
A1 Huang, Qiaojuan
A1 Zhou, Hui
A1 He, Qingyu
A1 Li, Bin
A1 Qu, Lianghu
A1 Yang, Jianhua
T1 TP53-inducible putative long noncoding RNAs encode functional polypeptides that suppress cell proliferation
JF Genome Research 
JO Genome Research 
YR 2022 
FD June 01 
VO 32 
IS 6 
SP 1026 
OP 1041 
DO 10.1101/gr.275831.121 
UL http://genome.cshlp.org/content/32/6/1026.abstract 
AB Polypeptides encoded by long noncoding 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 can 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 15 of these TP53-regulated lncRNAs encode peptides. Furthermore, several peptides were validated by mass spectrometry. Ten of the novel translational lncRNAs are directly inducible by TP53 in response to DNA damage. We show that the TP53-inducible peptides TP53LC02 and TP53LC04, but not their lncRNAs, can suppress cell proliferation. TP53LC04 peptide also has a function associated with cell proliferation by regulating the cell cycle in response to DNA damage. This study shows that TP53-regulated lncRNAs can encode new functional peptides, leading to the expansion of the TP53 tumor-suppressor network and providing novel potential targets for cancer therapy.