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

作者：Pin Wang, Yiquan Xue, Yanmei Han, Lin Li, Cong Wu, Sheng Xu, Zhengping Jiang, Junfang Xu, Qiuyan Liu, Xuetao Cao · 发表于：Science · 年份：2014 · DOI：10.1126/science.1251456 · 被引用次数：1172 · 研究领域：Cancer-related molecular mechanisms research、RNA Research and Splicing、interferon and immune responses

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.