期刊
BLOOD
卷 115, 期 1, 页码 133-139出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-09-242180
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资金
- Children's Research Institute at the Medical College of Wisconsin
- National Institutes of Health [HL090712]
- Advancing Healthier Wisconsin
- State of Wisconsin Breast Cancer Research postdoctoral fellowship
Recently, messenger RNAs in eukaryotes have shown to associate with antisense (AS) transcript partners that are often referred to as long noncoding RNAs (IncRNAs) 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 IncRNA in zebrafish, mouse, and humans. In embryonic zebrafish, tie-1AS IncRNA 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 IncRNA 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 IncRNA 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. (Blood. 2010;115:133-139)
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