title: A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo.
abstract: Recently, messenger RNAs in eukaryotes have shown to associate with antisense (AS) transcript partners that are often referred to as long noncoding RNAs (lncRNAs) whose function is largely unknown. Here, we have identified a natural AS transcript for tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-1 (tie-1), tie-1AS lncRNA in zebrafish, mouse, and humans. In embryonic zebrafish, tie-1AS lncRNA transcript is expressed temporally and spatially in vivo with its native target, the tie-1 coding transcript and in additional locations (ear and brain). The tie-1AS lncRNA selectively binds tie-1 mRNA in vivo and regulates tie-1 transcript levels, resulting in specific defects in endothelial cell contact junctions in vivo and in vitro. The ratio of tie-1 versus tie-1AS lncRNA is altered in human vascular anomaly samples. These results directly implicate noncoding RNA-mediated transcriptional regulation of gene expression as a fundamental control mechanism for physiologic processes, such as vascular development.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Developmental Vascular Biology Program, Children's Research Institute, Milwaukee, USA.
authors.forename: Keguo
authors.initials: K
authors.lastname: Li
authors.forename: Yannick
authors.initials: Y
authors.lastname: Blum
authors.forename: Anjali
authors.initials: A
authors.lastname: Verma
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.forename: Kallal
authors.initials: K
authors.lastname: Pramanik
authors.forename: Noah R
authors.initials: NR
authors.lastname: Leigh
authors.forename: Chang Z
authors.initials: CZ
authors.lastname: Chun
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Samant
authors.forename: Baofeng
authors.initials: B
authors.lastname: Zhao
authors.forename: Maija K
authors.initials: MK
authors.lastname: Garnaas
authors.forename: Mark A
authors.initials: MA
authors.lastname: Horswill
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stanhope
authors.forename: Paula E
authors.initials: PE
authors.lastname: North
authors.forename: Robert Q
authors.initials: RQ
authors.lastname: Miao
authors.forename: George A
authors.initials: GA
authors.lastname: Wilkinson
authors.forename: Markus
authors.initials: M
authors.lastname: Affolter
authors.forename: Ramani
authors.initials: R
authors.lastname: Ramchandran
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010641:Phenotype; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D042810:Receptor, TIE-1 / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014652:Vascular Diseases / Q000235:genetics / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016372:RNA, Antisense; D022661:RNA, Untranslated; D042461:Vascular Endothelial Growth Factor A; D029961:Zebrafish Proteins; D042810:Receptor, TIE-1; C467973:tie1 protein, zebrafish