Long noncoding RNAs in innate and adaptive immunity

Abstract

The differentiation and activation of both innate and adaptive immune cells is highly dependent on a coordinated set of transcriptional and post-transcriptional events. Chromatin-modifiers and transcription factors regulate the accessibility and transcription of immune genes, respectively. Immune cells also express miRNA and RNA-binding proteins that provide an additional layer of regulation at the mRNA level. However, long noncoding RNAs (lncRNAs), which have been primarily studied in the context of genomic imprinting, cancer, and cell differentiation, are now emerging as important regulators of immune cell differentiation and activation. In this review, we provide a brief overview of lncRNAs, their known functions in immunity, and discuss their potential to be more broadly involved in other aspects of the immune response.

Figure 1

Classification of lncRNA relative to protein-coding genes. Arrows indicate the direction of transcription. lncRNA contain non-coding exons (unfilled boxes). mRNA exons are composed of coding regions (filled boxes) and UTRs (unfilled boxes). Intronic lncRNA are located within an intron of a protein-coding gene in either direction and do not overlap with exons in the protein-coding gene. Divergent lncRNA/mRNA pairs are have proximal 5’-ends and are transcribed in opposite directions. Non-overlapping lncRNA do not overlap with protein-coding genes and are also referred to as intergenic or interleaved lncRNA. cisNATS are natural antisense transcripts that are complementary to an overlapping transcript. Here, the individual exons of the protein-coding gene have unique colors (blue, red, and green) and the colors of the cisNAT indicate corresponding regions of complementarity. transNATs are complementary to a non-overlapping transcript in a different genomic location (inter- or intra-chromosomal) where the colors indicate regions of complementarity. Adapted from Rinn and Chang [5]

Figure 2

Known and proposed functions of lncRNA in immunity. lncRNAs typically regulate transcription of a gene by forming complexes that bind a genomic region upstream of the transcription start site. lncRNA can potentially interact with other transcripts and regulate miRNA pathways, translation, splicing, and RNA turnover. lncRNAs with known molecular functions in immunity are colored black. Potential molecular functions for lncRNA in immunity are colored blue. Adapted from Hu et al [8]. lncRNA: long non-coding RNA, mRNA: messenger RNA, RNP: Ribonucleoprotein, hnRNPs: Heterogenous Ribonucleoproteins, NATs: Natural antisense transcripts.