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A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo.

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.

Pubmed ID: 19880500

Authors

  • Li K
  • Blum Y
  • Verma A
  • Liu Z
  • Pramanik K
  • Leigh NR
  • Chun CZ
  • Samant GV
  • Zhao B
  • Garnaas MK
  • Horswill MA
  • Stanhope SA
  • North PE
  • Miao RQ
  • Wilkinson GA
  • Affolter M
  • Ramchandran R

Journal

Blood

Publication Data

January 7, 2010

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL090712
  • Agency: NHLBI NIH HHS, Id: R01 HL090712
  • Agency: NHLBI NIH HHS, Id: R01 HL090712-03
  • Agency: NHLBI NIH HHS, Id: R01 HL102745

Mesh Terms

  • Animals
  • Endothelial Cells
  • Endothelium
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Loci
  • Humans
  • Intercellular Junctions
  • Mice
  • Neovascularization, Physiologic
  • Phenotype
  • RNA, Antisense
  • RNA, Untranslated
  • Receptor, TIE-1
  • Species Specificity
  • Vascular Diseases
  • Vascular Endothelial Growth Factor A
  • Zebrafish
  • Zebrafish Proteins