Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression
Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression
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DOI：
10.1038/ni.1902
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发表时间：
2010-08-01
影响因子：
30.5
通讯作者：
Heissmeyer, Vigo
中科院分区：
文献类型：
--
作者：
Glasmacher, Elke;Hoefig, Kai P.;Heissmeyer, Vigo
roquin控制诱导共刺激因子（inducible costimulator， ICOS）表达以预防自身免疫的分子机制尚不清楚。本研究表明，在辅助性T细胞中，roquin定位于加工(P)体并下调ICOS表达。这种抑制依赖于RNA解旋酶Rck，并且roquin与Rck和脱帽增强子Edc4相互作用，它们在mRNA脱帽过程中共同起作用。roquin中赋予p体定位的序列对于roquin介导的ICOS抑制是必不可少的。然而，这一过程不需要microrna或rna诱导沉默复合体（RISC）。相反，roquin直接结合ICOS mRNA，显示出对先前未识别的3‘非翻译区（3’ UTR）序列的内在偏好。我们的研究结果支持一个模型，其中roquin通过结合ICOS mRNA的3' UTR和与赋予转录后抑制的蛋白质相互作用来控制ICOS表达。
The molecular mechanism by which roquin controls the expression of inducible costimulator (ICOS) to prevent autoimmunity remains unsolved. Here we show that in helper T cells, roquin localized to processing (P) bodies and downregulated ICOS expression. The repression was dependent on the RNA helicase Rck, and roquin interacted with Rck and the enhancer of decapping Edc4, which act together in mRNA decapping. Sequences in roquin that confer P-body localization were essential for roquin-mediated ICOS repression. However, this process did not require microRNAs or the RNA-induced silencing complex (RISC). Instead, roquin bound ICOS mRNA directly, showing an intrinsic preference for a previously unrecognized sequence in the 3' untranslated region (3' UTR). Our results support a model in which roquin controls ICOS expression through binding to the 3' UTR of ICOS mRNA and by interacting with proteins that confer post-transcriptional repression.