title: Avian Leukosis Virus Activation of an Antisense RNA Upstream of TERT in B-Cell Lymphomas.
abstract: Avian leukosis virus (ALV) induces tumors by integrating its proviral DNA into the chicken genome and altering the expression of nearby genes via strong promoter and enhancer elements. Viral integration sites that contribute to oncogenesis are selected in tumor cells. Deep-sequencing analysis of B-cell lymphoma DNA confirmed that the telomerase reverse transcriptase (TERT) gene promoter is a common ALV integration target. Twenty-six unique proviral integration sites were mapped between 46 and 3,552 nucleotides (nt) upstream of the TERT transcription start site, predominantly in the opposite transcriptional orientation to TERT Transcriptome-sequencing (RNA-seq) analysis of normal bursa revealed a transcribed region upstream of TERT in the opposite orientation, suggesting the TERT promoter is bidirectional. This transcript appears to be an uncharacterized antisense RNA. We have previously shown that TERT expression is upregulated in tumors with integrations in the TERT promoter region. We now report that the viral promoter drives the expression of a chimeric transcript containing viral sequences spliced to exons 4 through 7 of this antisense RNA. Clonal expansion of cells with ALV integrations driving overexpression of the TERT antisense RNA suggest it may have a role in tumorigenesis.
  
  
  
  The data suggest that ALV integrations in the TERT promoter region drive the overexpression of a novel antisense RNA and contribute to the development of lymphomas.
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA BIOO Scientific, Austin, Texas, USA.
authors: Jiri
authors: J
authors: Nehyba
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Sanandan
authors: S
authors: Malhotra
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Shelby
authors: S
authors: Winans
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA Quantabio, Beverly, Massachusetts, USA.
authors: Thomas H
authors: TH
authors: O'Hare
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: James
authors: J
authors: Justice
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA klb@jhu.edu.
authors: Karen
authors: K
authors: Beemon
mesh_terms: D000818:Animals; D001353:Avian Leukosis / Q000235:genetics* / Q000821:virology*; D001354:Avian Leukosis Virus / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002645:Chickens; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000821:virology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D024363:Transcription Initiation Site / Q000502:physiology; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D016662:Virus Integration / Q000235:genetics
chemical_list: D016372:RNA, Antisense; D019098:Telomerase