Publication

Back to overview

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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2011
Author Kulkarni Smita, Savan Ram, Qi Ying, Gao Xiaojiang, Yuki Yuko, Bass Sara E, Martin Maureen P, Hunt Peter, Deeks Steven G, Telenti Amalio, Pereyra Florencia, Goldstein David, Wolinsky Steven, Walker Bruce, Young Howard A, Carrington Mary,
Project Host evolutionary genomics of HIV-1 and other retroviruses
Show all

Original article (peer-reviewed)

Journal Nature
Volume (Issue) 472(7344)
Page(s) 495 - 8
Title of proceedings Nature
DOI 10.1038/nature09914

Abstract

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.
-