Long Noncoding RNAs and Angiogenesis

• Editorials
• angiogenesis
• endothelial cell
• noncoding RNA

Article, see p 65

Accumulating evidence supports the notion that the mammalian genome is pervasively transcribed. A large proportion of the transcripts do not encode a protein and are thus regarded as noncoding RNAs. Based on their length, they can be divided into small RNAs (<200 nucleotides) and long noncoding RNAs (lncRNAs; >200 nucleotides).^1,2 LncRNAs can be encoded in the same or opposite strand to protein-coding DNA and can be either within or separate to protein-coding genes. They can be exported to the cytoplasm or remain in the nucleus. Although their function is not fully understood, lncRNAs have been reported to mediate the expression of other genes, affect the organization of the nucleus, and modify other RNAs.^1,2

In this issue of Circulation, Leisegang and colleagues³ identify a novel lncRNA that regulates angiogenesis. Previous work by this group highlighted the role of a histone demethylase, the protein JARID1B, in maintaining the angiogenic capacity of human umbilical vein endothelial cells.⁴ In the present study, the authors performed a transcriptomic screen following knockdown of JARID1B in human umbilical vein endothelial cells. They discovered a novel lncRNA, named MANTIS, to be strongly upregulated. MANTIS is located in the antisense strand of an intronic region of the gene for Annexin A4, a calcium and phospholipid binding protein. MANTIS is a nuclear lncRNA that is enriched in endothelial cells but also expressed in other cell types. Reducing MANTIS levels led to impaired endothelial sprouting, tube formation, and attenuated endothelial migration. It is notable that human umbilical …