Differential microRNA regulation of HLA-C expression and its association with HIV control.

Published

Journal Article

The HLA-C locus is distinct relative to the other classical HLA class I loci in that it has relatively limited polymorphism, lower expression on the cell surface, and more extensive ligand-receptor interactions with killer-cell immunoglobulin-like receptors. A single nucleotide polymorphism (SNP) 35 kb upstream of HLA-C (rs9264942; termed -35) associates with control of HIV, and with levels of HLA-C messenger RNA transcripts and cell-surface expression, but the mechanism underlying its varied expression is unknown. We proposed that the -35 SNP is not the causal variant for differential HLA-C expression, but rather is marking another polymorphism that directly affects levels of HLA-C. Here we show that variation within the 3' untranslated region (UTR) of HLA-C regulates binding of the microRNA hsa-miR-148 to its target site, resulting in relatively low surface expression of alleles that bind this microRNA and high expression of HLA-C alleles that escape post-transcriptional regulation. The 3' UTR variant associates strongly with control of HIV, potentially adding to the effects of genetic variation encoding the peptide-binding region of the HLA class I loci. Variation in HLA-C expression adds another layer of diversity to this highly polymorphic locus that must be considered when deciphering the function of these molecules in health and disease.

Full Text

Cited Authors

  • Kulkarni, S; Savan, R; Qi, Y; Gao, X; Yuki, Y; Bass, SE; Martin, MP; Hunt, P; Deeks, SG; Telenti, A; Pereyra, F; Goldstein, D; Wolinsky, S; Walker, B; Young, HA; Carrington, M

Published Date

  • April 17, 2011

Published In

Volume / Issue

  • 472 / 7344

Start / End Page

  • 495 - 498

PubMed ID

  • 21499264

Pubmed Central ID

  • 21499264

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature09914

Language

  • eng