Elsevier

Human Immunology

Volume 82, Issue 7, July 2021, Pages 532-540
Human Immunology

Review
Regulatory noncoding RNAs and the major histocompatibility complex

https://doi.org/10.1016/j.humimm.2020.06.005Get rights and content

Abstract

The Major Histocompatibility Complex (MHC) is a 4 Mbp genomic region located on the short arm of chromosome 6. The MHC region contains many key immune-related genes such as Human Leukocyte Antigens (HLAs). There has been a growing realization that, apart from MHC encoded proteins, RNAs derived from noncoding regions of the MHC—specifically microRNAs (miRNAs) and long noncoding RNAs (lncRNAs)—play a significant role in cellular regulation. Furthermore, regulatory noncoding RNAs (ncRNAs) derived from other parts of the genome fine-tune the expression of many immune-related MHC proteins. Although the field of ncRNAs of the MHC is a research area that is still in its infancy, ncRNA regulation of MHC genes has already been shown to be vital for immune function, healthy pregnancy and cellular homeostasis. Dysregulation of this intricate network of ncRNAs can lead to serious perturbations in homeostasis and subsequent disease.

Section snippets

Introduction:

The Major Histocompatibility Complex (MHC) locus is home to more than 200 genes and is one of the most gene-rich and sequence-variable regions of the human genome. The MHC is located on the short arm of chromosome 6 and encodes a large number of genes involved in innate and adaptive immunity [1]. The 4 Mbp genomic region which encodes the MHC contains the highest density of disease/trait associated variants among all regions of similar size in the human genome [1]. Recent research suggests

MHC derived long noncoding RNAs

Among a number of functionalities, ranging from well-understood to unknown, noncoding regions may code for RNAs, such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). lncRNAs are non–protein-coding transcripts of more than 200 nucleotides. It is estimated that human DNA encodes more than 30,000 different lncRNAs, which may arise as antisense transcripts complementary to coding genes or from intergenic regions, introns or pseudogenes [4], [5].

Therefore, lncRNAs can be classified as

Conclusion

MHC biology and its impact on human physiology have long been widely recognized. However, the discovery that MHC non-coding regions may also play important roles in physiology and disease pathways has only been recently recognized. Despite recent reports indicating the considerable importance of MHC-derived lncRNAs and miRNAs, the full significance of MHC non-coding RNAs is far from clearly understood. With respect to lncRNAs, we know only that the MHC encodes a large number of such ncRNAs,

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by institutional funds from The Children’s Hospital of Philadelphia to D.M.

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