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.

journal_name

Blood

journal_title

Blood

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

doi

10.1182/blood-2009-09-242180

subject

Has Abstract

pub_date

2010-01-07 00:00:00

pages

133-9

issue

1

eissn

0006-4971

issn

1528-0020

pii

blood-2009-09-242180

journal_volume

115

pub_type

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