RNA-mediated sequestration of the RNA helicase eIF4A by pateamine A inhibits translation initiation
RNA-mediated sequestration of the RNA helicase eIF4A by pateamine A inhibits translation initiation
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DOI：
10.1016/j.chembiol.2006.10.005
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发表时间：
2006-12-01
影响因子：
--
通讯作者：
Pelletier, Jerry
中科院分区：
文献类型：
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作者：
Bordeleau, Marie-Eve;Cencic, Regina;Pelletier, Jerry
真核起始因子4A（eIF 4A）是RNA解旋酶DEAD-盒家族的成员之一，其成员参与RNA代谢的许多方面。eIF 4A被认为通过解旋存在于5'非翻译区的二级结构促进43 S前起始复合物与mRNA的结合。Pateamine A是一种翻译起始的小分子抑制剂，通过刺激eIF 4A活性以不寻常的方式起作用。在此，我们报告的说明的帕特拉明的行动方式。我们证明，Pateamine A是二聚化的化学诱导剂，迫使eIF 4A和RNA之间的接合，并阻止eIF 4A参与翻译起始的核糖体募集步骤。
Eukaryotic initiation factor 4A (eIF4A) is a member of the DEAD-box family of putative RNA helicases whose members are involved in many aspects of RNA metabolism. eIF4A is thought to facilitate binding of 43S preinitiation complexes to mRNAs by unwinding secondary structures present in the 5' untransiated region. Pateamine A, a small-molecule inhibitor of translation initiation, acts in an unusual manner by stimulating eIF4A activity. Herein, we report the elucidation of pateamine's mode of action. We demonstrate that Pateamine A is a chemical inducer of dimerization that forces an engagement between eIF4A and RNA and prevents eIF4A from participating in the ribosome-recruitment step of translation initiation.