ProPred1: prediction of promiscuous MHC Class-I binding sites

BackgroundTo control gene expression, microRNAs (miRNAs) are of key importance and their deregulation is associated with the development and progression of various cancer types. In this context, a discordant messenger RNA/protein expression pointing to extensive post-transcriptional regulation of major histocompatibility complex (MHC) class I molecules was already shown. However, only a very limited number of miRNAs targeting these molecules have yet been identified. Despite an increasing evidence of coding sequence (CDS)-located miRNA binding sites, there exists so far, no detailed study of the interaction of miRNAs with the CDS of MHC class I molecules.MethodsUsing an MS2-tethering approach in combination with small RNA sequencing, a number of putative miRNAs binding to the CDS of human leukocyte antigen (HLA)-G were identified. These candidate miRNAs were extensively screened for their effects in the HLA-G-positive JEG3 cell line. Due to the high sequence similarity between HLA-G and classical MHC class I molecules, the impact of HLA-G candidate miRNAs on HLA class I surface expression was also analyzed. The Cancer Genome Atlas data were used to correlate candidate miRNAs and HLA class I gene expression.ResultsTransfection of candidate miRNAs revealed that miR-744 significantly downregulates HLA-G protein levels. In contrast, overexpression of the candidate miRNAs miR-15, miR-16, and miR-424 sharing the same seed sequence resulted in an unexpected upregulation of HLA-G. Comparable results were obtained for classical MHC class I members after transfection of miRNA mimics into HEK293T cells. Analyses of The Cancer Genome Atlas data sets for miRNA and MHC class I expression further validated the results.ConclusionsOur data expand the knowledge about MHC class I regulation and showed for the first time an miRNA-dependent control of MHC class I antigens mediated by the CDS. CDS-located miRNA binding sites could improve the general use of miRNA-based therapeutic approaches as these sites are highly independent of structural variations (e.g. mutations) in the gene body. Surprisingly, miR-16 family members promoted MHC class I expression potentially in a gene activation-like mechanism.

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MHC class I allele diversity in cynomolgus macaques of Vietnamese origin

PeerJ ◽

10.7717/peerj.7941 ◽

2019 ◽

Vol 7 ◽

pp. e7941

Author(s):

Shuting Huang ◽

Xia Huang ◽

Shuang Li ◽

Mingjun Zhu ◽

Min Zhuo

Keyword(s):

Mhc Class I ◽

Binding Sites ◽

Macaca Fascicularis ◽

Peptide Binding ◽

Cynomolgus Macaque ◽

Class I ◽

Histocompatibility Complex ◽

Cynomolgus Macaques ◽

Mhc Alleles ◽

Potential Recombination Event

Cynomolgus macaques (Macaca fascicularis, Mafa) have been used as important experimental animal models for carrying out biomedical researches. The results of biomedical experiments strongly depend on the immunogenetic background of animals, especially on the diversity of major histocompatibility complex (MHC) alleles. However, there is much less information available on the polymorphism of MHC class I genes in cynomolgus macaques, than is currently available for humans. In this study, we have identified 40 Mafa-A and 60 Mafa-B exons 2 and 3 sequences from 30 unrelated cynomolgus macaques of Vietnamese origin. Among these alleles, 28 are novel. As for the remaining 72 known alleles, 15 alleles are shared with other cynomolgus macaque populations and 32 are identical to alleles previously reported in other macaque species. A potential recombination event was observed between Mafa-A1*091:02 and Mafa-A1*057:01. In addition, the Mafa-A1 genes were found to be more diverse than human HLA-A and the functional residues for peptide binding sites (PBS) or TCR binding sites (TBS) in Mafa-A1 have greater variability than that for non-PBS or non-TBS regions. Overall, this study provides important information on the diversity of Mafa-A and Mafa-B alleles from Vietnamese origin, which may help researchers to choose the most appropriate animals for their studies.

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MHC Class I Regulation: The Origin Perspective

Cancers ◽

10.3390/cancers12051155 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1155 ◽

Cited By ~ 1

Author(s):

Alicja Sznarkowska ◽

Sara Mikac ◽

Magdalena Pilch

Keyword(s):

Mhc Class I ◽

Binding Sites ◽

Therapeutic Interventions ◽

Class I ◽

Mhc I ◽

Origin And Evolution ◽

Non Coding Rnas ◽

Regulatory Rnas ◽

Tumor Types ◽

Complex Regulatory Network

Viral-derived elements and non-coding RNAs that build up “junk DNA” allow for flexible and context-dependent gene expression. They are extremely dense in the MHC region, accounting for flexible expression of the MHC I, II, and III genes and adjusting the level of immune response to the environmental stimuli. This review brings forward the viral-mediated aspects of the origin and evolution of adaptive immunity and aims to link this perspective with the MHC class I regulation. The complex regulatory network behind MHC expression is largely controlled by virus-derived elements, both as binding sites for immune transcription factors and as sources of regulatory non-coding RNAs. These regulatory RNAs are imbalanced in cancer and associate with different tumor types, making them promising targets for diagnostic and therapeutic interventions.

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