A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo. Blood 2010 Jan 07;115(1):133-9
Date
11/03/2009Pubmed ID
19880500Pubmed Central ID
PMC2803688DOI
10.1182/blood-2009-09-242180Scopus ID
2-s2.0-74949140605 (requires institutional sign-in at Scopus site) 134 CitationsAbstract
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.
Author List
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 RAuthors
Keguo Li MD, PhD Research Scientist I in the Surgery department at Medical College of WisconsinPaula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsEndothelial 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
