帽结合蛋白 4EHP 通过 microRNAs 影响翻译沉默。
Cap-binding protein 4EHP effects translation silencing by microRNAs.
机构信息
Goodman Cancer Research Center, McGill University, Montreal, QC H3A 1A3, Canada.
Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada.
出版信息
Proc Natl Acad Sci U S A. 2017 May 23;114(21):5425-5430. doi: 10.1073/pnas.1701488114. Epub 2017 May 9.
Abstract
MicroRNAs (miRNAs) play critical roles in a broad variety of biological processes by inhibiting translation initiation and by destabilizing target mRNAs. The CCR4-NOT complex effects miRNA-mediated silencing, at least in part through interactions with 4E-T (eIF4E transporter) protein, but the precise mechanism is unknown. Here we show that the cap-binding eIF4E-homologous protein 4EHP is an integral component of the miRNA-mediated silencing machinery. We demonstrate that the cap-binding activity of 4EHP contributes to the translational silencing by miRNAs through the CCR4-NOT complex. Our results show that 4EHP competes with eIF4E for binding to 4E-T, and this interaction increases the affinity of 4EHP for the cap. We propose a model wherein the 4E-T/4EHP interaction engenders a closed-loop mRNA conformation that blocks translational initiation of miRNA targets.
摘要
微小 RNA（miRNA）通过抑制翻译起始和破坏靶 mRNA 来在广泛的生物过程中发挥关键作用。CCR4-NOT 复合物对 miRNA 介导的沉默有影响，至少部分是通过与 4E-T（eIF4E 转运蛋白）蛋白相互作用，但确切的机制尚不清楚。在这里，我们表明帽结合 eIF4E 同源蛋白 4EHP 是 miRNA 介导的沉默机制的一个组成部分。我们证明，4EHP 的帽结合活性通过 CCR4-NOT 复合物有助于 miRNA 介导的翻译沉默。我们的结果表明，4EHP 与 eIF4E 竞争与 4E-T 的结合，并且这种相互作用增加了 4EHP 对帽的亲和力。我们提出了一个模型，其中 4E-T/4EHP 相互作用产生了封闭的 mRNA 构象，阻止了 miRNA 靶标的翻译起始。
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