Long Noncoding RNA–MicroRNA Pathway Controlling Nuclear Factor IA , A Novel Atherosclerosis Modifier Gene

In the current issue, Hu et al1 provide evidence for the transcription factor nuclear factor 1A ( NFIA ) as a novel atherosclerosis candidate gene, which is regulated through expression of the long noncoding RNA (lncRNA) RP5-833A20.1 , embedded in intron 2 of NFIA , and microRNA (miRNA) hsa-miR-382-5p. In addition to providing compelling evidence for a role of NFIA in atherogenesis, the article is important for strengthening the concept of lncRNAs as master-regulators of this frequent disease. See accompanying article on page 87 lncRNAs are a class of RNAs gaining increasing attention in biomedical research. They lack an open reading frame and are distinguished from other classes of noncoding RNAs, such as miRNAs, by an arbitrary size limit of >200 bp.2 Until now, >10 000 mammalian lncRNAs have been discovered across the genome and it has only been recognized recently that lncRNAs constitute an important layer of transcriptional regulation.3 In a hypothesis-free approach, the authors used expression arrays in a THP-1 foam cell model and identified several differentially expressed mRNAs and lncRNAs. They subsequently focused on NFIA , which overlapped with the genomic position of a yet uncharacterized lncRNA, designated RP5-833A20.1 …