Long Non-Coding RNAs and Immunity


Long Non-Coding RNAs and Immunity

A longstanding observation in biology is that while the number of protein coding genes has remained relatively stable across multicellular organisms, the genomic content of non-coding DNA increases with the developmental complexity of organisms. This seemingly puzzling finding, termed the G-value paradox, suggests that the degree of regulatory control exerted by non-coding regions over protein-coding genes determines phenotypic complexity, which has increased throughout evolution. In support of this inference, a number of high-throughput sequencing projects have recently shown that a great proportion of the mammalian non-coding genome comprises an immense network of cis-regulatory elements such as promoters, enhancers, and super-enhancers. Strikingly, these consortia also showed that nearly 70% of the human non-coding genome shows evidence of transcriptional activity. The function of the majority of these non-coding transcripts remains mostly unknown. Nevertheless, several classes of non-coding RNAs have been found to contribute to the transcriptional and epigenetic regulation of gene expression programs.

Among these functional non-coding RNAs, long non-coding RNAs, i.e. lncRNAs, are the most abundant and have been extensively studied in recent years. Although still in its infancy, the systematic study of lncRNAs has already begun to reveal diverse functions for these molecules in regulating immune cell development, function and survival. For example, lncRNAs such as lincRNA-Cox2, Lethe, PACER and lnc13 have all been shown to regulate innate immune responses. Moreover, a single nucleotide polymorphism in lnc13 is associated with susceptibility to coeliac disease, highlighting the importants of lncRNAs in human immune diseases.

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