Lin Daisy, Pestova Tatyana V, Hellen Christopher U T, Tiedge Henri
The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, State University of New York, Health Science Center at Brooklyn, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Mol Cell Biol. 2008 May;28(9):3008-19. doi: 10.1128/MCB.01800-07. Epub 2008 Mar 3.
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.
越来越多的证据表明，翻译抑制因子参与突触处蛋白质合成的调控，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，它在起始水平上抑制翻译。然而，BC1抑制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）的催化活性，一种依赖ATP的RNA解旋酶，作为BC1介导的翻译控制的靶点。BC1 RNA特异性地阻断eIF4A的RNA双链解旋活性，但同时刺激其ATP酶活性。BC200 RNA，灵长类特有的BC1对应物，以相同的方式靶向eIF4A活性，从而使ATP水解与RNA双链解旋脱钩。在体内，BC1 RNA抑制具有5'二级结构的报告mRNA的翻译。eIF4A机制使BC RNA处于调节神经元蛋白质合成的中心位置。
