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

作者：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, Nu Zhang · 发表于：Nature Communications · 年份：2018 · DOI：10.1038/s41467-018-06862-2 · 被引用次数：828 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、Cancer-related molecular mechanisms research

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.