Human IL12RB1 expression is allele-biased and produces a novel IL12 response regulator.
Human IL12RB1 expression is allele-biased and produces a novel IL12 response regulator.
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DOI：
10.1038/s41435-018-0023-2
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发表时间：
2019-03
影响因子：
5
通讯作者：
Robinson RT
中科院分区：
文献类型：
--
作者：
Reeme AE;Claeys TA;Aggarwal P;Turner AJ;Routes JM;Broeckel U;Robinson RT
人IL 12 RB 1是一种常染色体基因，对分枝杆菌疾病抗性和T细胞分化至关重要。使用原代人组织和PBMC，我们证明了肺和T细胞IL 12 RB 1表达是等位基因偏向的，并且细胞表达一个IL 12 RB 1等位基因的程度不受激活的影响。此外，在其表达后，IL 12 RB 1前mRNA被加工成IL 12 RB 1同种型1（IL 12 R β1，一种IL 12-反应性的正调节剂）或IL 12 RB 1同种型2（一种迄今为止未知功能的蛋白质）。T细胞将前mRNA加工成同种型1或同种型2的选择由IL 12 RB 1外显子9-10剪接与IL 12 RB 1外显子9 b剪接的基因内竞争以及IL 12 RB 1外显子9 b相关的多聚腺苷酸化位点控制。异质性核核糖核蛋白H（hnRNP H）结合附近的调节多聚腺苷酸化位点，但不需要外显子9 b多聚腺苷酸化。最后，microRNA介导的敲低实验证明IL 12 RB 1同种型2促进T细胞IL 12应答。总的来说，我们的数据支持这样的模型，其中人IL 12 RB 1的组织表达是等位基因偏向的，并产生hnRNP H结合的前mRNA，其加工产生新的IL 12应答调节剂。
Human IL12RB1 is an autosomal gene that is essential for mycobacterial disease resistance and T cell differentiation. Using primary human tissue and PBMCs, we demonstrate that lung and T cell IL12RB1 expression is allele-biased, and the extent to which cells express one IL12RB1 allele is unaffected by activation. Furthermore, following its expression the IL12RB1 pre-mRNA is processed into either IL12RB1 Isoform 1 (IL12Rβ1, a positive regulator of IL12-responsiveness) or IL12RB1 Isoform 2 (a protein of heretofore unknown function). T cells’ choice to process pre-mRNA into Isoform 1 or Isoform 2 is controlled by intragenic competition of IL12RB1 exon 9-10 splicing with IL12RB1 exon 9b splicing, as well as an IL12RB1 exon 9b-associated polyadenylation site. Heterogeneous nuclear ribonucleoprotein H (hnRNP H) binds near the regulated polyadenylation site, but is not required for exon 9b polyadenylation. Finally, microRNA-mediated knockdown experiments demonstrated that IL12RB1 Isoform 2 promotes T cell IL12 responses. Collectively, our data support a model wherein tissue expression of human IL12RB1 is allele-biased and produces an hnRNP H bound pre-mRNA, the processing of which generates a novel IL12 response regulator.
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DOI：
10.1084/jem.20021769
发表时间：
2003-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fieschi C;Dupuis S;Catherinot E;Feinberg J;Bustamante J;Breiman A;Altare F;Baretto R;Le Deist F;Kayal S;Koch H;Richter D;Brezina M;Aksu G;Wood P;Al-Jumaah S;Raspall M;Da Silva Duarte AJ;Tuerlinckx D;Virelizier JL;Fischer A;Enright A;Bernhöft J;Cleary AM;Vermylen C;Rodriguez-Gallego C;Davies G;Blütters-Sawatzki R;Siegrist CA;Ehlayel MS;Novelli V;Haas WH;Levy J;Freihorst J;Al-Hajjar S;Nadal D;De Moraes Vasconcelos D;Jeppsson O;Kutukculer N;Frecerova K;Caragol I;Lammas D;Kumararatne DS;Abel L;Casanova JL
通讯作者：
Casanova JL
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.4
作者：
Calado, Dinis Pedro;Paixao, Tiago;Haury, Matthias
通讯作者：
Haury, Matthias
影响因子：
4.8
作者：
Fogel, BL;McNally, MT
通讯作者：
McNally, MT
影响因子：
6.4
作者：
Dhiman, Neelam;Ovsyannikova, Inna G.;Jacobson, Robert M.
通讯作者：
Jacobson, Robert M.