A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma

Maolei Zhang, Kun Zhao, Xiaoping Xu, Yibing Yang, Sheng Yan, Ping Wei, Hui Liu, Jianbo Xu, Feizhe Xiao, Huangkai Zhou, Xuesong Yang, Nunu Huang, Jinglei Liu, Kejun He, Keping Xie, Gong Zhang, Suyun Huang and Nu Zhang ()
Additional contact information
Maolei Zhang: First Affiliated Hospital of Sun Yat-sen University
Kun Zhao: First Affiliated Hospital of Sun Yat-sen University
Xiaoping Xu: First Affiliated Hospital of Sun Yat-sen University
Yibing Yang: First Affiliated Hospital of Sun Yat-sen University
Sheng Yan: First Affiliated Hospital of Sun Yat-sen University
Ping Wei: Fudan University
Hui Liu: First Affiliated Hospital of Sun Yat-sen University
Jianbo Xu: First Affiliated Hospital of Sun Yat-sen University
Feizhe Xiao: First Affiliated Hospital of Sun Yat-sen University
Huangkai Zhou: First Affiliated Hospital of Sun Yat-sen University
Xuesong Yang: First Affiliated Hospital of Sun Yat-sen University
Nunu Huang: First Affiliated Hospital of Sun Yat-sen University
Jinglei Liu: First Affiliated Hospital of Sun Yat-sen University
Kejun He: First Affiliated Hospital of Sun Yat-sen University
Keping Xie: University of Texas MD Anderson Cancer Center
Gong Zhang: Jinan University
Suyun Huang: University of Texas MD Anderson Cancer Center
Nu Zhang: First Affiliated Hospital of Sun Yat-sen University

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract Circular RNAs (circRNAs) are a large class of transcripts in the mammalian genome. Although the translation of circRNAs was reported, additional coding circRNAs and the functions of their translated products remain elusive. Here, we demonstrate that an endogenous circRNA generated from a long noncoding RNA encodes regulatory peptides. Through ribosome nascent-chain complex-bound RNA sequencing (RNC-seq), we discover several peptides potentially encoded by circRNAs. We identify an 87-amino-acid peptide encoded by the circular form of the long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) that suppresses glioblastoma cell proliferation in vitro and in vivo. This peptide directly interacts with polymerase associated factor complex (PAF1c) and inhibits the transcriptional elongation of multiple oncogenes. The expression of this peptide and its corresponding circRNA are decreased in glioblastoma compared with the levels in normal tissues. Our results establish the existence of peptides encoded by circRNAs and demonstrate their potential functions in glioblastoma tumorigenesis.

Date: 2018
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DOI: 10.1038/s41467-018-06862-2

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