2. Academic Validation
  3. A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma

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

  • Nat Commun. 2018 Oct 26;9(1):4475. doi: 10.1038/s41467-018-06862-2.
Maolei Zhang 1 2,  Kun Zhao 1 2,  Xiaoping Xu 1 2,  Yibing Yang 1 2,  Sheng Yan 1 2 3,  Ping Wei 4,  Hui Liu 5,  Jianbo Xu 6,  Feizhe Xiao 7,  Huangkai Zhou 1 2 8,  Xuesong Yang 1 2,  Nunu Huang 1 2,  Jinglei Liu 1 2,  Kejun He 1 2,  Keping Xie 9,  Gong Zhang 10,  Suyun Huang 11 12,  Nu Zhang 13 14
Affiliations

Affiliations

  • 1 Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, PR China.
  • 2 Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, 510080, Guangdong, PR China.
  • 3 Department of Neurosurgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530000, Guangxi Province, PR China.
  • 4 Department of Pathology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, PR China.
  • 5 Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China.
  • 6 Department of Gastroenterology Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China.
  • 7 Department of Scientific Research Section, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, PR China.
  • 8 Guangzhou Gene Denovo Biotechnology Co. Ltd, Guangzhou, 510006, PR China.
  • 9 Department of Gastroenterology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • 10 Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, PR China.
  • 11 Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • 12 Program in Cancer Biology, University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, 77030, USA.
  • 13 Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, PR China. [email protected].
  • 14 Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, 510080, Guangdong, PR China. [email protected].
PMID: 30367041 DOI: 10.1038/s41467-018-06862-2
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.

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