title: MYCNOS functions as an antisense RNA regulating MYCN.
abstract: Amplification or overexpression of neuronal MYC (MYCN) is associated with poor prognosis of human neuroblastoma. Three isoforms of the MYCN protein have been described as well as a protein encoded by an antisense transcript (MYCNOS) that originates from the opposite strand at the MYCN locus. Recent findings suggest that some antisense long non-coding RNAs (lncRNAs) can play a role in epigenetically regulating gene expression. Here we report that MYCNOS transcripts function as a modulator of the MYCN locus, affecting MYCN promoter usage and recruiting various proteins, including the Ras GTPase-activating protein-binding protein G3BP1, to the upstream MYCN promoter. Overexpression of MYCNOS results in a reduction of upstream MYCN promoter usage and increased MYCN expression, suggesting that the protein-coding MYCNOS also functions as a regulator of MYCN ultimately controlling MYCN transcriptional variants. The observations presented here demonstrate that protein-coding transcripts can regulate gene transcription and can tether regulatory proteins to target loci.
authors.affiliation: a Molecular and Experimental Medicine ; The Scripps Research Institute ; La Jolla , CA USA.
authors.forename: Nadia
authors.initials: N
authors.lastname: Vadie
authors.forename: Sheena
authors.initials: S
authors.lastname: Saayman
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lenox
authors.forename: Amanda
authors.initials: A
authors.lastname: Ackley
authors.forename: Mathew
authors.initials: M
authors.lastname: Clemson
authors.forename: Jon
authors.initials: J
authors.lastname: Burdach
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hart
authors.forename: Peter K
authors.initials: PK
authors.lastname: Vogt
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Morris
mesh_terms: D001374:Azacitidine / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004265:DNA Helicases; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008957:Models, Genetic; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D016372:RNA, Antisense / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors; D000067776:RNA Recognition Motif Proteins; D016372:RNA, Antisense; C012589:trichostatin A; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases; D001374:Azacitidine
keywords: G3BP1; MAP4; RNA; Transcriptional regulation; bidirectional promoter; neuroblastoma