The STAT3-Binding Long Noncoding RNA lnc-DC Controls Human Dendritic Cell Differentiation

Abstract

Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes; however, few have been identified that regulate immune cell differentiation and function. Here, we identified lnc-DC, which was exclusively expressed in human conventional dendritic cells (DCs). Knockdown of lnc-DC impaired DC differentiation from human monocytes in vitro and from mouse bone marrow cells in vivo and reduced capacity of DCs to stimulate T cell activation. lnc-DC mediated these effects by activating the transcription factor STAT3 (signal transducer and activator of transcription 3). lnc-DC bound directly to STAT3 in the cytoplasm, which promoted STAT3 phosphorylation on tyrosine-705 by preventing STAT3 binding to and dephosphorylation by SHP1. Our work identifies a lncRNA that regulates DC differentiation and also broadens the known mechanisms of lncRNA action.

Expanding the functional role of long noncoding RNAs

“…The findings presented within this study are in line with previous reports suggesting that phosphorylation of STAT3 is regulated by a lncRNA, lnc-DC [5].…”

Long Noncoding RNAs in Atherosclerosis

“…SENCR knockdown decreased myocardin al 72) identified a dendritic cell-specific lncRNA termed lnc-DC playing a critical role in the differentiation of dendritic cells from human monocytes and mouse bone marrow, a cell type playing important roles in atherosclerosis 73) . Another study has shown that lncRNA APOA1-AS function as a negative transcriptional regulator and distinct histone methylation patterns modulator of APOA1 74) , a major component of HDL particles associated with reduced atherosclerosis 75) .…”

Novel Aberrations Uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma Using Whole Transcriptome Sequencing

“…Most microarray-based transcriptome analyses will for example miss a large proportion of long noncoding RNAs (lncRNAs), which are involved in almost all known cellular processes (10)(11)(12)(13)(14), and are important in cancer biology, as shown by the number of functional characterized lncRNAs involved in carcinogenesis (15). In EAC, only two lncRNAs have been reported (16,17), and no systematic approach identifying lncRNAs dysregulation at different stages of Barrett's disease and EAC development has been published so far.…”