title: VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer.
abstract: BACKGROUND
  The function of the non-coding portion of the human genome remains one of the most important questions of our time. Its vast complexity is exemplified by the recent identification of an unusual and notable component of the transcriptome - very long intergenic non-coding RNAs, termed vlincRNAs.
  
  
  RESULTS
  Here we identify 2,147 vlincRNAs covering 10 percent of our genome. We show they are present not only in cancerous cells, but also in primary cells and normal human tissues, and are controlled by canonical promoters. Furthermore, vlincRNA promoters frequently originate from within endogenous retroviral sequences. Strikingly, the number of vlincRNAs expressed from endogenous retroviral promoters strongly correlates with pluripotency or the degree of malignant transformation. These results suggest a previously unknown connection between the pluripotent state and cancer via retroviral repeat-driven expression of vlincRNAs. Finally, we show that vlincRNAs can be syntenically conserved in humans and mouse and their depletion using RNAi can cause apoptosis in cancerous cells.
  
  
  CONCLUSIONS
  These intriguing observations suggest that vlincRNAs could create a framework that combines many existing short ESTs and lincRNAs into a landscape of very long transcripts functioning in the regulation of gene expression in the nucleus. Certain types of vlincRNAs participate at specific stages of normal development and, based on analysis of a limited set of cancerous and primary cell lines, they appear to be co-opted by cancer-associated transcriptional programs. This provides additional understanding of transcriptome regulation during the malignant state, and could lead to additional targets and options for its reversal.
authors.forename: Georges
authors.initials: G
authors.lastname: St Laurent
authors.forename: Dmitry
authors.initials: D
authors.lastname: Shtokalo
authors.forename: Biao
authors.initials: B
authors.lastname: Dong
authors.forename: Michael R
authors.initials: MR
authors.lastname: Tackett
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Fan
authors.forename: Sandra
authors.initials: S
authors.lastname: Lazorthes
authors.forename: Estelle
authors.initials: E
authors.lastname: Nicolas
authors.forename: Nianli
authors.initials: N
authors.lastname: Sang
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Triche
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McCaffrey
authors.forename: Weidong
authors.initials: W
authors.lastname: Xiao
authors.forename: Philipp
authors.initials: P
authors.lastname: Kapranov
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D020077:Endogenous Retroviruses / Q000235:genetics*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D058977:Molecular Sequence Annotation; D009369:Neoplasms / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D020079:Terminal Repeat Sequences / Q000235:genetics
chemical_list: D062085:RNA, Long Noncoding; D008156:Luciferases