ZFIN ID: ZDB-PUB-091120-8
A non-coding antisense RNA in tie-1 locus regulates tie-1 function in vivo
Li, K., Blum, Y., Verma, A., Liu, Z., Pramanik, K., Leigh, N.R., Chun, C.Z., Samant, G.V., Zhao, B., Garnaas, M.K., Horswill, M.A., Stanhope, S.A., North, P.E., Miao, R.Q., Wilkinson, G.A., Affolter, M., and Ramchandran, R.
Date: 2010
Source: Blood   115(1): 133-139 (Journal)
Registered Authors: Affolter, Markus, Chun, Chang Zoon, Garnaas, Maija, Horswill, Mark, Leigh, Noah, Li, Keguo, Ramchandran, Ramani, Samant, Ganesh, Verma, Anjali
Keywords: none
MeSH Terms:
  • Animals
  • Endothelial Cells/drug effects
  • Endothelial Cells/metabolism
  • Endothelial Cells/pathology
  • Endothelium/drug effects
  • Endothelium/metabolism
  • Endothelium/pathology
  • Gene Expression Profiling
  • Gene Expression Regulation/drug effects
  • Genetic Loci/genetics*
  • Humans
  • Intercellular Junctions/drug effects
  • Intercellular Junctions/metabolism
  • Intercellular Junctions/pathology
  • Mice
  • Neovascularization, Physiologic/drug effects
  • Phenotype
  • RNA, Antisense/genetics*
  • RNA, Antisense/metabolism
  • RNA, Untranslated/genetics*
  • RNA, Untranslated/metabolism
  • Receptor, TIE-1/genetics
  • Receptor, TIE-1/metabolism
  • Species Specificity
  • Vascular Diseases/genetics
  • Vascular Diseases/pathology
  • Vascular Endothelial Growth Factor A/pharmacology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 19880500 Full text @ Blood
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 & 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 vs. tie-1AS lncRNA is altered in human vascular anomaly samples. These results directly implicate non-coding RNA mediated transcriptional regulation of gene expression as a fundamental control mechanism for physiological process such as vascular development.