The long non-coding RNA PARROT is an upstream regulator of c-Myc and affects proliferation and translation

Long non-coding RNAs are important regulators of gene expression and signaling pathways. The expression of long ncRNAs is dysregulated in cancer and other diseases. The identification and characterization of long ncRNAs is often challenging due to their low expression level and localization to chromatin. Here, we identify a functional long ncRNA, PARROT (Proliferation Associated RNA and Regulator Of Translation) transcribed by RNA polymerase II and expressed at a relatively high level in a number of cell lines. The PARROT long ncRNA is associated with proliferation in both transformed and normal cell lines. We characterize the long ncRNA PARROT as an upstream regulator of c-Myc affecting cellular proliferation and translation using RNA sequencing and mass spectrometry following depletion of the long ncRNA. PARROT is repressed during senescence of human mammary epithelial cells and overexpressed in some cancers, suggesting an important association with proliferation through regulation of c-Myc. With this study, we add to the knowledge of cytoplasmic functional long ncRNAs and extent the long ncRNA-Myc regulatory network in transformed and normal cells.

[1]  R. Winzen,et al.  IL-1-induced post-transcriptional mechanisms target overlapping translational silencing and destabilizing elements in IκBζ mRNA. , 2016, The Journal of Biological Chemistry.

[2]  A. Rosenwald,et al.  MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells , 2015, Proceedings of the National Academy of Sciences.

[3]  U. A. Ørom,et al.  Insight into miRNA biogenesis with RNA sequencing , 2015, Oncotarget.

[4]  C. Croce,et al.  MYC-repressed long noncoding RNAs antagonize MYC-induced cell proliferation and cell cycle progression , 2015, Oncotarget.

[5]  Reuven Agami,et al.  Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA , 2015, Nature Communications.

[6]  K. Kok,et al.  Long noncoding RNAs as a novel component of the Myc transcriptional network , 2015, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  S. Dhanasekaran,et al.  The landscape of long noncoding RNAs in the human transcriptome , 2015, Nature Genetics.

[8]  O. Kepp,et al.  A long non-coding RNA links calreticulin-mediated immunogenic cell removal to RB1 transcription , 2015, Oncogene.

[9]  I. Petersen,et al.  Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data , 2015, Genome Biology.

[10]  D. Meierhofer,et al.  Metabolome and proteome profiling of complex I deficiency induced by rotenone. , 2015, Journal of proteome research.

[11]  Maite Huarte,et al.  Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature , 2014, Nature Communications.

[12]  S. Srivastava,et al.  A long noncoding RNA connects c-Myc to tumor metabolism , 2014, Proceedings of the National Academy of Sciences.

[13]  T. Conrad,et al.  Microprocessor activity controls differential miRNA biogenesis In Vivo. , 2014, Cell reports.

[14]  Yoshimasa Tanaka,et al.  Small Molecules Targeting c-Myc Oncogene: Promising Anti-Cancer Therapeutics , 2014, International journal of biological sciences.

[15]  Z. Lou,et al.  The Long Non-Coding RNA GAS5 Cooperates with the Eukaryotic Translation Initiation Factor 4E to Regulate c-Myc Translation , 2014, PloS one.

[16]  Junhui Ge,et al.  Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus , 2014, Cell Research.

[17]  U. A. Ørom,et al.  Molecular mechanisms of long ncRNAs in neurological disorders , 2014, Front. Genet..

[18]  Feng Yang,et al.  Long non‐coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c‐Myc mRNA stability , 2014, The FEBS journal.

[19]  J. Rinn,et al.  Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2 , 2013, Genome Biology.

[20]  S. Oliviero,et al.  Role of the AP-1 transcription factor FOSL1 in endothelial cells adhesion and migration , 2013, Cell adhesion & migration.

[21]  D. Bartel,et al.  lincRNAs: Genomics, Evolution, and Mechanisms , 2013, Cell.

[22]  Nicholas T Ingolia,et al.  Genome-wide annotation and quantitation of translation by ribosome profiling. , 2013, Current protocols in molecular biology.

[23]  S. Sauer,et al.  Protein Sets Define Disease States and Predict In Vivo Effects of Drug Treatment* , 2013, Molecular & Cellular Proteomics.

[24]  Feng Yang,et al.  Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma , 2013, Journal of Cancer Research and Clinical Oncology.

[25]  R. Elkon,et al.  eRNAs are required for p53-dependent enhancer activity and gene transcription. , 2013, Molecular cell.

[26]  L. Lipovich,et al.  Activity-Dependent Human Brain Coding/Noncoding Gene Regulatory Networks , 2012, Genetics.

[27]  Nadav S. Bar,et al.  Landscape of transcription in human cells , 2012, Nature.

[28]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[29]  Chi V Dang,et al.  MYC on the Path to Cancer , 2012, Cell.

[30]  Bo Li,et al.  RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells , 2012, Oncogene.

[31]  C. Glass,et al.  Reprogramming Transcription via Distinct Classes of Enhancers Functionally Defined by eRNA , 2011, Nature.

[32]  I. Bièche,et al.  ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  J. Rinn,et al.  Large non-coding RNAs: missing links in cancer? , 2010, Human molecular genetics.

[34]  T. Derrien,et al.  Long Noncoding RNAs with Enhancer-like Function in Human Cells , 2010, Cell.

[35]  J. Rinn,et al.  A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response , 2010, Cell.

[36]  R. Pulido,et al.  Differential Up-regulation of MAP Kinase Phosphatases MKP3/DUSP6 and DUSP5 by Ets2 and c-Jun Converge in the Control of the Growth Arrest Versus Proliferation Response of MCF-7 Breast Cancer Cells to Phorbol Ester* , 2010, The Journal of Biological Chemistry.

[37]  S. Raguz,et al.  Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. , 2010, Molecular cell.

[38]  D. Felsher,et al.  MYC as a regulator of ribosome biogenesis and protein synthesis , 2010, Nature Reviews Cancer.

[39]  Aaron R. Quinlan,et al.  BIOINFORMATICS APPLICATIONS NOTE , 2022 .

[40]  Davis J. McCarthy,et al.  edgeR: a Bioconductor package for differential expression analysis of digital gene expression data , 2009, Bioinform..

[41]  C. Dang,et al.  MYC-Induced Cancer Cell Energy Metabolism and Therapeutic Opportunities , 2009, Clinical Cancer Research.

[42]  Heidi S Feiler,et al.  Molecular distinctions between stasis and telomere attrition senescence barriers shown by long-term culture of normal human mammary epithelial cells. , 2009, Cancer research.

[43]  R. Hass,et al.  Cellular senescence of human mammary epithelial cells (HMEC) is associated with an altered MMP-7/HB-EGF signaling and increased formation of elastin-like structures , 2009, Mechanisms of Ageing and Development.

[44]  M. Mann,et al.  MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification , 2008, Nature Biotechnology.

[45]  D. Taatjes,et al.  Cooperative activity of cdk8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3 , 2008, The EMBO journal.

[46]  S. Reddy,et al.  FRA-1 proto-oncogene induces lung epithelial cell invasion and anchorage-independent growth in vitro, but is insufficient to promote tumor growth in vivo. , 2007, Cancer research.

[47]  T. Schlange,et al.  Novel c‐MYC target genes mediate differential effects on cell proliferation and migration , 2007, EMBO reports.

[48]  Igor Jurisica,et al.  The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. , 2006, Cancer research.

[49]  M. Baccarini,et al.  Raf-1 sets the threshold of Fas sensitivity by modulating Rok-α signaling , 2005, The Journal of cell biology.

[50]  M. Nieto,et al.  The Snail genes as inducers of cell movement and survival: implications in development and cancer , 2005, Development.

[51]  Ravi Salgia,et al.  The role of ephrins and Eph receptors in cancer. , 2004, Cytokine & growth factor reviews.

[52]  G. Prendergast,et al.  Actin' up: RhoB in cancer and apoptosis , 2001, Nature Reviews Cancer.

[53]  J. Nishihira,et al.  Macrophage migration inhibitory factor (MIF): its essential role in the immune system and cell growth. , 2000, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[54]  K. Kaibuchi,et al.  Phosphorylation of Adducin by Rho-Kinase Plays a Crucial Role in Cell Motility , 1999, The Journal of cell biology.

[55]  O. Kepp,et al.  A long non-coding RNA links calreticulin-mediated immunogenic cell removal to RB 1 transcription , 2015 .

[56]  U. Narayanan,et al.  Novel DNA damage checkpoints mediating cell death induced by the NEDD8-activating enzyme inhibitor MLN4924. , 2013, Cancer research.