MHC I-associated peptides preferentially derive from transcripts bearing miRNA response elements
MHC I-associated peptides preferentially derive from transcripts bearing miRNA response elements
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DOI：
10.1182/blood-2012-02-412593
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发表时间：
2012-06-28
期刊：
影响因子：
20.3
通讯作者：
Perreault, Claude
中科院分区：
文献类型：
--
作者：
Granados, Diana Paola;Yahyaoui, Wafaa;Perreault, Claude
MHC I相关肽（MIPs）在正常的稳态和各种病理条件下发挥重要作用。MIP主要来源于缺陷核糖体产物（DRiP），这是新生蛋白质的一个子集，其未能实现适当的构象，并且其物理性质仍然难以捉摸。在本研究中，我们使用高通量的蛋白质组学和转录组学的方法来解开的结构和生物起源的人EBV感染的B淋巴细胞上的HLA-A和HLA-B B分子提出的MIP。我们发现，虽然HLA不同的主题提出了独特的MIP来自不同的蛋白质，这些MIP来自蛋白质的功能相互关联，并涉及类似的生物途径。其次，人B细胞的MIP库没有显示出对保守的多态性基因组序列的偏好，优先来源于丰富的转录本，并向细胞表面传递细胞类型特异性签名。最后，我们发现MIP优先来自带有miRNA反应元件的转录本。此外，尽管HLA不同受试者的MIP由不同的转录本编码，但这些转录本受大多数相似的miRNA调控。我们的数据支持一种新兴的模型，其中转录本产生MIP取决于其丰度和DRiP速率，这在很大程度上受miRNA的调控。（血。2012;119（26）：e181-e191）
MHC I-associated peptides (MIPs) play an essential role in normal homeostasis and diverse pathologic conditions. MIPs derive mainly from defective ribosomal products (DRiPs), a subset of nascent proteins that fail to achieve a proper conformation and the physical nature of which remains elusive. In the present study, we used high-throughput proteomic and transcriptomic methods to unravel the structure and biogenesis of MIPs presented by HLA-A and HLA-B molecules on human EBV-infected B lymphocytes from 4 patients. We found that although HLA-different subjects present distinctive MIPs derived from different proteins, these MIPs originate from proteins that are functionally interconnected and implicated in similar biologic pathways. Secondly, the MIP repertoire of human B cells showed no bias toward conserved versus polymorphic genomic sequences, were derived preferentially from abundant transcripts, and conveyed to the cell surface a cell-type-specific signature. Finally, we discovered that MIPs derive preferentially from transcripts bearing miRNA response elements. Furthermore, whereas MIPs of HLA-disparate subjects are coded by different sets of transcripts, these transcripts are regulated by mostly similar miRNAs. Our data support an emerging model in which the generation of MIPs by a transcript depends on its abundance and DRiP rate, which is regulated to a large extent by miRNAs. (Blood. 2012;119(26):e181-e191)