Differential microRNA regulation of HLA-C expression and its association with HIV control.
Differential microRNA regulation of HLA-C expression and its association with HIV control.
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DOI：
10.1038/nature09914
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发表时间：
2011-04-28
期刊：
影响因子：
64.8
通讯作者：
Carrington, Mary
中科院分区：
文献类型：
--
作者：
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
HLA-C 基因座相对于其他经典 HLA I 类基因座的独特之处在于，它具有相对有限的多态性、细胞表面表达较低以及与杀伤细胞免疫球蛋白样受体 (KIR) 更广泛的配体-受体相互作用。 HLA-C（rs9264942；称为-35）上游35Kb处的单核苷酸多态性（SNP）与HIV的控制以及HLA-C mRNA转录物和细胞表面表达的水平相关，但其不同表达的机制尚不清楚。我们提出-35 SNP 并不是 HLA-C 表达差异的因果变异，而是标记了另一种直接影响 HLA-C 水平的多态性。在这里，我们发现 HLA-C 3'非翻译区内的变异调节 microRNA Hsa-miR-148a 与其靶位点的结合，导致结合该 microRNA 的等位基因表面表达相对较低，而逃避转录后调控的 HLA-C 等位基因高表达。 3'UTR 变异与 HIV 的控制密切相关，可能会增加编码 HLA I 类基因座肽结合区的遗传变异的影响。 HLA-C 表达的变异为这个高度多态性基因座增加了另一层多样性，在破译这些分子在健康和疾病中的功能时必须考虑这一点。
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 (KIR). A single nucleotide polymorphism (SNP) 35Kb upstream of HLA-C (rs9264942; termed −35) associates with control of HIV, and with levels of HLA-C mRNA 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 of HLA-C regulates binding of the microRNA Hsa-miR-148a 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.
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影响因子：
15.3
作者：
ZEMMOUR, J;PARHAM, P
通讯作者：
PARHAM, P
影响因子：
9.2
作者：
Braud, VM;Allan, DSJ;McMichael, AJ
通讯作者：
McMichael, AJ
DOI：
10.1084/jem.181.6.2085
发表时间：
1995-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
McCutcheon JA;Gumperz J;Smith KD;Lutz CT;Parham P
通讯作者：
Parham P
影响因子：
56.9
作者：
Giraldez, AJ;Mishima, Y;Schier, AF
通讯作者：
Schier, AF
影响因子：
5.4
作者：
SNARY, D;BARNSTABLE, CJ;CRUMPTON, MJ
通讯作者：
CRUMPTON, MJ