The introduction of RNA-DNA differences underlies interindividual variation in the human IL12RB1 mRNA repertoire.
The introduction of RNA-DNA differences underlies interindividual variation in the human IL12RB1 mRNA repertoire.
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RNA-DNA 差异的引入是人类 IL12RB1 mRNA 库个体间变异的基础。
DOI：
10.1073/pnas.1515978112
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发表时间：
2015
影响因子：
11.1
通讯作者：
Robinson,RichardT
中科院分区：
文献类型：
--
作者：
Turner,AmyJ;Aggarwal,Praful;Miller,HalliE;Waukau,Jill;Routes,JohnM;Broeckel,Ulrich;Robinson,RichardT
人白介素12和白介素23(IL12/23)影响多种疾病的易感性或抵抗力。然而，IL12/23敏感性个体差异的原因仍不清楚。在此，我们报道了在人外周血单个核细胞和炎症肺中，大多数白细胞介素12受体β1(IL12RB1)β包含大量的RNADNA差异(RDd)，这些差异集中在IL12R mRNA1‘Rdna与IL12p40的S结合所必需的序列中，IL12RB1RNAs是IL-12和IL-23共同的蛋白质亚基。IL12RB1RDNAs包括多种RDD型，可以通过下一代测序和经典Sanger测序检测到。作为这些RDDS的结果，由此产生的IL12Rβ1蛋白具有改变的氨基酸序列，而不能仅基于基因组DNA测序来预测。重要的是，在IL12RB1mRNAs中引入RDDS负性调节IL12Rβ1‘S与IL12p40的结合，并且对激活敏感。总之，这些结果表明，将RDDS引入个体的IL12RB1mRNA谱系是IL12/23敏感性的一个新的决定因素。
Human interleukin 12 and interleukin 23 (IL12/23) influence susceptibility or resistance to multiple diseases. However, the reasons underlying individual differences in IL12/23 sensitivity remain poorly understood. Here we report that in human peripheral blood mononuclear cells (PBMCs) and inflamed lungs, the majority of interleukin-12 receptor β1 (IL12RB1) mRNAs contain a number of RNA-DNA differences (RDDs) that concentrate in sequences essential to IL12Rβ1’s binding of IL12p40, the protein subunit common to both IL-12 and IL-23.IL12RB1RDDs comprise multiple RDD types and are detectable by next-generation sequencing and classic Sanger sequencing. As a consequence of these RDDs, the resulting IL12Rβ1 proteins have an altered amino acid sequence that could not be predicted on the basis of genomic DNA sequencing alone. Importantly, the introduction of RDDs intoIL12RB1mRNAs negatively regulates IL12Rβ1’s binding of IL12p40 and is sensitive to activation. Collectively, these results suggest that the introduction of RDDs into an individual’sIL12RB1mRNA repertoire is a novel determinant of IL12/23 sensitivity.