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,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 +18 more
TLDR
A 87-amino-acid peptide encoded by the circular form of the long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) is identified that can reduce glioblastoma proliferation via interaction with PAF1 which sequentially inhibits the transcriptional elongation of some oncogenes.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.read more
Citations
More filters
Journal ArticleDOI
The biogenesis, biology and characterization of circular RNAs.
Lasse Sommer Kristensen,Maria S. Andersen,Lotte V. W. Stagsted,Karoline K. Ebbesen,Thomas B. Hansen,Jørgen Kjems +5 more
TL;DR: Advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.
Journal ArticleDOI
MicroRNAs and complex diseases: from experimental results to computational models.
TL;DR: Twenty state-of-the-art computational models of predicting miRNA-disease associations from different perspectives are reviewed, including five feasible and important research schemas, and future directions for further development of computational models are summarized.
Journal ArticleDOI
Translation and functional roles of circular RNAs in human cancer.
TL;DR: The works on circRNA translation will open a hidden human proteome, and enhance us to understand the importance of circRNAs in human cancer, which has been poorly explored so far.
Journal ArticleDOI
Circular RNA-protein interactions: functions, mechanisms, and identification.
TL;DR: The current knowledge regarding circRNA-protein interactions and the methods used to identify and characterize these interactions are reviewed and new insights are summarized into the potential mechanisms underlying these interactions.
Journal ArticleDOI
Circular RNAs in Cancer: Biogenesis, Function, and Clinical Significance.
TL;DR: The biogenesis, turnover, and involvements of circRNAs in cancer are summarized and their potential as diagnostic biomarkers or therapeutic targets are discussed.
References
More filters
Journal ArticleDOI
Fast gapped-read alignment with Bowtie 2
TL;DR: Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
Journal ArticleDOI
TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions
Daehwan Kim,Daehwan Kim,Geo Pertea,Cole Trapnell,Cole Trapnell,Harold Pimentel,Kelley Ryan Matthew,Steven L. Salzberg,Steven L. Salzberg +8 more
TL;DR: TopHat2 is described, which incorporates many significant enhancements to TopHat, and combines the ability to identify novel splice sites with direct mapping to known transcripts, producing sensitive and accurate alignments, even for highly repetitive genomes or in the presence of pseudogenes.
Journal ArticleDOI
Circular RNAs are a large class of animal RNAs with regulatory potency
Sebastian Memczak,Marvin Jens,Antigoni Elefsinioti,Francesca Torti,Janna Krueger,Agnieszka Rybak,Luisa Maier,Sebastian D. Mackowiak,Lea H. Gregersen,Mathias Munschauer,Alexander Loewer,Ulrike Ziebold,Markus Landthaler,Christine Kocks,Ferdinand le Noble,Nikolaus Rajewsky +15 more
TL;DR: It is found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7.
Journal ArticleDOI
Natural RNA circles function as efficient microRNA sponges
Thomas B. Hansen,Trine I. Jensen,Bettina Hjelm Clausen,Jesper B. Bramsen,Bente Finsen,Christian Kroun Damgaard,Jørgen Kjems +6 more
TL;DR: This study serves as the first functional analysis of a naturally expressed circular RNA, ciRS-7, which contains more than 70 selectively conserved miRNA target sites, and is highly and widely associated with Argonaute proteins in a miR-7-dependent manner.
Journal ArticleDOI
Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1
Roel G.W. Verhaak,Katherine A. Hoadley,Elizabeth Purdom,Victoria Wang,Yuan-yuan Qi,Matthew D. Wilkerson,C. Ryan Miller,Li Ding,Todd R. Golub,Jill P. Mesirov,Gabriele Alexe,Michael S. Lawrence,Michael O'Kelly,Pablo Tamayo,Barbara A. Weir,Stacey Gabriel,Wendy Winckler,Supriya Gupta,Lakshmi Jakkula,Heidi S. Feiler,J. Graeme Hodgson,C. David James,Jann N. Sarkaria,Cameron Brennan,Ari B. Kahn,Paul T. Spellman,Richard K. Wilson,Terence P. Speed,Terence P. Speed,Joe W. Gray,Matthew Meyerson,Gad Getz,Charles M. Perou,Charles M. Perou,D. Neil Hayes +34 more
TL;DR: A robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes is described and multidimensional genomic data is integrated to establish patterns of somatic mutations and DNA copy number.