Autoimmune targeting of key components of RNA interference.
Autoimmune targeting of key components of RNA interference.
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RNA干扰关键组件的自身免疫性靶向。
DOI：
10.1186/ar1959
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发表时间：
2006
影响因子：
4.9
通讯作者：
Chan EK
中科院分区：
文献类型：
--
作者：
Jakymiw A;Ikeda K;Fritzler MJ;Reeves WH;Satoh M;Chan EK
RNA干扰(RNAi)是一种进化上保守的机制，参与基因转录后沉默。这一过程基于与短干扰RNAs(SiRNAs)或microRNAs(MiRNAs)的互补性而导致mRNAs的降解或翻译抑制。最近，特定miRNAs的差异表达和miRNA合成途径的中断被认为与癌症有关；然而，它们在自身免疫性疾病中的作用仍然很大程度上尚不清楚。在这里，我们报道了来自风湿病患者的抗SU自身抗体和在自身免疫的小鼠模型中识别人类ArgAerte(AGO)蛋白hAgo2，它是RNAi途径中的催化核心酶。更具体地说，91%(20/22)的人抗SU血清免疫共沉淀出全长重组hAgo2蛋白。在Hep-2细胞中的间接免疫荧光研究表明，抗SU自身抗体靶向被确认为GW小体(GWB)或哺乳动物P小体的细胞质病灶，这些结构最近与RNAi功能有关。此外，抗SU血清还能够免疫沉淀RNAi途径的其他关键成分，包括hAgo1、-3、-4和Disher。综上所述，这些结果表明了对RNAi途径的组成部分的自身免疫反应，这可能意味着先天抗病毒反应参与了自身抗体产生的发病机制。
RNA interference (RNAi) is an evolutionarily conserved mechanism that is involved in the post-transcriptional silencing of genes. This process elicits the degradation or translational inhibition of mRNAs based on the complementarity with short interfering RNAs (siRNAs) or microRNAs (miRNAs). Recently, differential expression of specific miRNAs and disruption of the miRNA synthetic pathway have been implicated in cancer; however, their role in autoimmune disease remains largely unknown. Here, we report that anti-Su autoantibodies from human patients with rheumatic diseases and in a mouse model of autoimmunity recognize the human Argonaute (Ago) protein, hAgo2, the catalytic core enzyme in the RNAi pathway. More specifically, 91% (20/22) of the human anti-Su sera were shown to immunoprecipitate the full-length recombinant hAgo2 protein. Indirect immunofluorescence studies in HEp-2 cells demonstrated that anti-Su autoantibodies target cytoplasmic foci identified as GW bodies (GWBs) or mammalian P bodies, structures recently linked to RNAi function. Furthermore, anti-Su sera were also capable of immunoprecipitating additional key components of the RNAi pathway, including hAgo1, -3, -4, and Dicer. Together, these results demonstrate an autoimmune response to components of the RNAi pathway which could potentially implicate the involvement of an innate anti-viral response in the pathogenesis of autoantibody production.
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影响因子：
21.3
作者：
Jakymiw, A;Lian, SL;Chan, EKL
通讯作者：
Chan, EKL
DOI：
10.1084/jem.180.6.2341
发表时间：
1994-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Satoh M;Reeves WH
通讯作者：
Reeves WH
影响因子：
4.5
作者：
Eystathioy, T;Jakymiw, A;Fritzler, MJ
通讯作者：
Fritzler, MJ
影响因子：
32.4
作者：
Bennasser, Y;Le, SY;Jeang, KT
通讯作者：
Jeang, KT
影响因子：
21.3
作者：
Sen, GL;Blau, HM
通讯作者：
Blau, HM