Gene regulation in the immune system by long noncoding RNAs

Abstract

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression in the immune system. Studies have shown that lncRNAs are expressed in a highly lineage-specific manner and control the differentiation and function of innate and adaptive cell types. In this Review, we focus on mechanisms used by lncRNAs to regulate genes encoding products involved in the immune response, including direct interactions with chromatin, RNA and proteins. In addition, we address new areas of lncRNA biology, such as the functions of enhancer RNAs, circular RNAs and chemical modifications to RNA in cellular processes. We emphasize critical gaps in knowledge and future prospects for the roles of lncRNAs in the immune system and autoimmune disease.

Figure 1

General lncRNA mechanism. lncRNAs function by interacting with DNA, RNA and proteins.

Figure 2

lncRNAs in the differentiation and function of immune cells. (a) lncRNAs can regulate the differentiation of precursor cells into mature cells, as well as the subsequent activation of those mature cells. (b) The selected lncRNAs presented here control the maturation of HSCs into mature immune-cell subtypes and control the subsequent activation of those cell types.

Figure 3

New mechanisms: RNA modification and circular RNA. (a) RNA with m⁶A and intron modifications forms a secondary structure for forward splicing into linear RNA. (b) RNA with m⁶A but no intron modification forms a secondary structure for back splicing into circRNA. (c) The presence or lack of modifications leads to differential recognition by the immune system.