Immunobiology of Long Noncoding RNAs

The discovery of long noncoding RNAs (lncRNA) has provided a new perspective on gene regulation in diverse biological contexts. lncRNAs are remarkably versatile molecules that interact with RNA, DNA, or proteins to promote or restrain the expression of protein-coding genes. Activation of immune cells is associated with dynamic changes in expression of genes, the products of which combat infectious microorganisms, initiate repair, and resolve inflammatory responses in cells and tissues. Recent evidence indicates that lncRNAs play important roles in directing the development of diverse immune cells and controlling the dynamic transcriptional programs that are a hallmark of immune cell activation. The importance of these molecules is underscored by their newly recognized roles in inflammatory diseases. Here, researchers from the University of Massachusetts Medical School discuss the contribution of lncRNAs in the development and activation of immune cells and their roles in immune-related diseases. They also discuss challenges faced in identifying biological functions for this large and complex class of genes.

 Mechanism of action for lncRNAs

lncRNAs mediate their molecular functions through a multitude of mechanisms in (a) the cytoplasm or (b) the nucleus. In the cytoplasm, lncRNAs act through RNA-protein(e.g., NRON and lnc-DC) or RNA-RNA (e.g., Uchl1-AS and linc-MD1) interactions. NRON and lnc-D Cact as molecular scaffolds for the transcription factors NFAT and STAT3, respectively. Uchl1-AS interacts with target mRNAs through base pairing to enhance their translation. In the nucleus, lncRNAs can act in cis or trans.(b) Morrbid interacts with PRC2 to repress transcription of the neighboring gene, Bim(Bcl2l11), in cis in short-lived myeloid cells such as neutrophils and monocytes. A lncRNA can interact with its protein partner as a guide (e.g., lincRNA-EPS:hnRNPL), scaffold (e.g., RMRP interaction with DDX5 and RORγt),or decoy molecule (e.g., Lethe: NF-κB p65) to mediate its molecular functions. Abbreviations: linc-MD1, lincRNA associated with muscle differentiation 1; Uchl1, ubiquitin carboxy-terminal hydrolase L1.