Translational control by a small RNA: Dendritic BC1 RNA targets the eukaryotic initiation factor 4A helicase mechanism
Translational control by a small RNA: Dendritic BC1 RNA targets the eukaryotic initiation factor 4A helicase mechanism
复制标题
DOI：
10.1128/mcb.01800-07
复制
发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Tiedge, Henri
中科院分区：
文献类型：
--
作者：
Lin, Daisy;Pestova, Tatyana V.;Tiedge, Henri
越来越多的证据表明，翻译抑制因子参与了突触蛋白质合成的调节，从而为突触强度的长期可塑性调节提供了基础。树突状BC1 RNA是一种非蛋白质编码RNA，在起始水平抑制翻译。然而，BC1阻遏的分子机制仍然未知。在这里，我们确定了真核起始因子4A（eIF4A），ATP依赖性RNA解旋酶，作为BC1介导的翻译控制的目标的催化活性。BC1 RNA特异性阻断eIF4A的RNA双链体解旋活性，但同时刺激其ATP酶活性。BC200 RNA（灵长类特异性BC1对应物）以相同的方式靶向eIF4A活性，结果使ATP水解与RNA双链体解旋脱钩。在体内，BC1 RNA抑制具有5 '二级结构的报告mRNA的翻译。eIF4A机制将BC RNA置于中心位置以调节神经元中的蛋白质合成。
Translational repressors, increasing evidence suggests, participate in the regulation of protein synthesis at the synapse, thus providing a basis for the long-term plastic modulation of synaptic strength. Dendritic BC1 RNA is a non-protein-coding RNA that represses translation at the level of initiation. However, the molecular mechanism of BC1 repression has remained unknown. Here we identify the catalytic activity of eukaryotic initiation factor 4A (eIF4A), an ATP-dependent RNA helicase, as a target of BC1-mediated translational control. BC1 RNA specifically blocks the RNA duplex unwinding activity of eIF4A but, at the same time, stimulates its ATPase activity. BC200 RNA, the primate-specific BC1 counterpart, targets eIF4A activity in identical fashion, as a result decoupling ATP hydrolysis from RNA duplex unwinding. In vivo, BC1 RNA represses translation of a reporter mRNA with 5' secondary structure. The eIF4A mechanism places BC RNAs in a central position to modulate protein synthesis in neurons.