Long noncoding RNAs (lncRNAs) can regulate gene expression. In Science, Fitzgerald and colleagues identify lincRNA-Cox2 as a regulatory lncRNA expressed in macrophages. This lincRNA, named for the proximity of its gene with Cox2, is upregulated by activation of the pathway consisting of Toll-like receptors, the adaptor MyD88 and the transcription factor NF-κB. Expression of lincRNA-Cox2 affects hundreds of genes, but notably those involved in immune responses. lincRNA-Cox2 downregulates Ccl5 and various interferon-stimulated genes and upregulates Tlr1, Il6 and Il23a. It associates with the heterogeneous nuclear ribonucleoproteins hnRNP-A/B and hnRNP-A2/B1. Knockdown of those or LincRNA-Cox2 relieves the repression of Ccl5 and interferon-stimulated genes, although the spectrum of genes regulated by lincRNA-Cox2 and hnRNPs does not completely overlap. These findings introduce another layer of transcriptional regulation on inducible genes that control immunological function.

Science 341, 789–792 (2013)