Institute of Genetics and Biophysics 'A. Buzzati Traverso', CNR, Via Pietro Castellino 111, 80131, Naples, Italy.
Nucleic Acids Res. 2011 Sep 1;39(16):7263-75. doi: 10.1093/nar/gkr278. Epub 2011 May 29.
Major histocompatibility complex class II mRNAs encode heterodimeric proteins involved in the presentation of exogenous antigens during an immune response. Their 3'UTRs bind a protein complex in which we identified two factors: EBP1, an ErbB3 receptor-binding protein and DRBP76, a double-stranded RNA binding nuclear protein, also known as nuclear factor 90 (NF90). Both are well-characterized regulatory factors of several mRNA molecules processing. Using either EBP1 or DRBP76/NF90-specific knockdown experiments, we established that the two proteins play a role in regulating the expression of HLA-DRA, HLA-DRB1 and HLA-DQA1 mRNAs levels. Our study represents the first indication of the existence of a functional unit that includes different transcripts involved in the adaptive immune response. We propose that the concept of 'RNA operon' may be suitable for our system in which MHCII mRNAs are modulated via interaction of their 3'UTR with same proteins.
主要组织相容性复合体 II 类 mRNA 编码异二聚体蛋白,参与免疫反应中外源抗原的呈递。它们的 3'UTR 与一种蛋白质复合物结合,我们在其中鉴定了两种因子:EBP1,一种 ErbB3 受体结合蛋白和 DRBP76,一种双链 RNA 结合核蛋白,也称为核因子 90(NF90)。这两种蛋白都是几种 mRNA 分子加工的特征调节因子。通过使用 EBP1 或 DRBP76/NF90 特异性敲低实验,我们确定这两种蛋白在调节 HLA-DRA、HLA-DRB1 和 HLA-DQA1 mRNA 水平的表达中发挥作用。我们的研究首次表明存在一个功能单元,该单元包含参与适应性免疫反应的不同转录本。我们提出,“RNA 操纵子”的概念可能适用于我们的系统,其中 MHCII mRNA 通过其 3'UTR 与相同的蛋白质相互作用进行调节。