对HLA-C表达的微RNA差异调节及其与HIV控制的关联
Smita Kulkarni1, Ram Savan, Ying Qi
1Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, USA.
Nature
|April 19, 2011
概括
在HLA-C中,一种新的3'未翻译区域 (UTR) 变异调节微RNA结合,影响细胞表面表达. 这一发现揭示了HLA-C的存在.
科学领域:
- 免疫遗传学 免疫遗传学
- 分子生物学分子生物学
- 人类白细胞抗原 (HLA) 研究
背景情况:
- HLA-C位点表现出独特的特征,包括有限的多态性,较低的细胞表面表达,以及与杀手细胞免疫球蛋白类受体的广泛相互作用.
- HLA-C (rs9264942) 上游的单核酸多态 (SNP) 与HIV控制和HLA-C表达水平有关,但其精确的机制尚不清楚.
研究的目的:
- 研究遗传变异影响HLA-C表达水平的机制.
- 确定上游SNP是否是致病变体或影响HLA-C表达的致病变体标记.
主要方法:
- 对HLA-C.的3'非翻译区域 (UTR) 内变异的分析.
- 研究微RNA与HLA-C 3' UTR变异的结合亲和力.
- 3' UTR变异与HLA-C表达水平和HIV控制的相关性.
主要成果:
- 在HLA-C 3' UTR中的变异直接调节微RNA hsa-miR-148.8 的结合.
- 与hsa-miR-148结合亲和度较高的等位基因表现出较低的表面表达.
- 脱离这种微RNA的转录后调节的等位基因表现出高的HLA-C表达.
- 确定的3' UTR变异与控制艾滋病毒感染有很强的关联.
结论:
- 通过微RNA与HLA-C 3' UTR结合的转录后调节是HLA-C表面表达水平的关键决定因素.
- HLA-C 3' UTR中的遗传变异有助于控制HIV,可能补充HLA类I结区域的影响.
- 了解HLA-C表达变异性对于解读它在健康和疾病中的作用至关重要.
相关概念视频
MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...


