Long noncoding RNAs (lncRNAs) have been linked to the regulation of chromatin structure, gene expression and mRNA translation; however, lncRNAs might serve other regulatory roles in the cell. In Science, Wang et al. describe a distinct regulatory mechanism for lnc-DC, a lncRNA that is expressed exclusively in conventional dendritic cells (DCs) and is induced when monocytes differentiate into DCs. lnc-DC is required for the functional presentation of antigens and T cell–priming activities, as well as for the expression of IL-12 by DCs. RNA-mediated interference of lnc-DC results in diminished expression of hundreds of DC-associated genes, which suggests its regulatory role might differ from that of previously described lncRNAs. Instead, lnc-DC is associated with the transcription factor STAT3 in the cytoplasm. Loss of lnc-DC leads to less phosphorylation of STAT3 at Tyr705, whereas ectopic expression of lnc-DC leads to more of this phosphorylation. lnc-DC seems to maintain activated STAT3 by protecting against dephosphorylation by the phosphatase SHP-1, which indicates a unique function for lncRNAs. Whether lnc-DC-mediated regulation might also explain the distinct roles of STAT3 in various contexts deserves further investigation.

Science 344, 310–313 (2014)