Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, PR China.
Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, 510080, Guangdong, PR China.
Nat Commun. 2018 Oct 26;9(1):4475. doi: 10.1038/s41467-018-06862-2.
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.
环状 RNA（circRNAs）是哺乳动物基因组中一类很大的转录本。尽管已经报道了 circRNAs 的翻译，但额外的编码 circRNAs 及其翻译产物的功能仍然难以捉摸。在这里，我们证明了一种来自长非编码 RNA 的内源性 circRNA 编码调节肽。通过核糖体新生链复合物结合 RNA 测序（RNC-seq），我们发现了几个可能由 circRNAs 编码的肽。我们鉴定出一种由长基因间非蛋白编码 RNA p53 诱导转录物（LINC-PINT）的环状形式编码的 87 个氨基酸肽，该肽在体外和体内抑制神经胶质瘤细胞的增殖。这种肽直接与聚合酶相关因子复合物（PAF1c）相互作用，并抑制多个癌基因的转录延伸。与正常组织相比，这种肽及其相应的 circRNA 在神经胶质瘤中的表达降低。我们的研究结果确立了 circRNAs 编码的肽的存在，并证明了它们在神经胶质瘤肿瘤发生中的潜在功能。
