A ribosome-specialized translation initiation pathway is required for cap-dependent translation of vesicular stomatitis virus mRNAs
A ribosome-specialized translation initiation pathway is required for cap-dependent translation of vesicular stomatitis virus mRNAs
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DOI：
10.1073/pnas.1216454109
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发表时间：
2013-01-02
影响因子：
11.1
通讯作者：
Whelan, Sean P. J.
中科院分区：
文献类型：
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作者：
Lee, Amy Si-Ying;Burdeinick-Kerr, Rebeca;Whelan, Sean P. J.
起始是所有生物体翻译控制的主要目标。传统上认为真核生物翻译的调控通过起始因子和RNA结构发生。在这里，我们的特点是转录特异性的翻译起始机制，是由核糖体介导的。通过研究水泡性口炎病毒（VSV），我们确定了核糖体大亚基蛋白rpL40作为VSV帽依赖性翻译所必需的，但不是散装细胞或内部核糖体进入位点驱动的翻译。这种要求在单负性病毒目的成员中是保守的，包括麻疹病毒和狂犬病病毒。多核糖体分析和体外重建的起始证明，rpL40是需要通过顺式调控元件的VSV mRNA上的80 S形成。使用深度测序，我们进一步揭示了一个子集的细胞转录选择性敏感rpL40耗尽，这表明VSV可能已经篡夺了内源性翻译途径。总之，这些发现表明，在蛋白质合成过程中，核糖体作为一个翻译调节剂以外的催化作用。
Initiation is the primary target of translational control for all organisms. Regulation of eukaryotic translation is traditionally thought to occur through initiation factors and RNA structures. Here, we characterize a transcript-specific translation initiation mechanism that is mediated by the ribosome. By studying vesicular stomatitis virus (VSV), we identify the large ribosomal subunit protein rpL40 as requisite for VSV cap-dependent translation but not bulk cellular or internal ribosome entry site-driven translation. This requirement is conserved among members of the order Mononegavirales, including measles virus and rabies virus. Polysome analyses and in vitro reconstitution of initiation demonstrate that rpL40 is required for 80S formation on VSV mRNAs through a cis-regulatory element. Using deep sequencing, we further uncover a subset of cellular transcripts that are selectively sensitive to rpL40 depletion, suggesting VSV may have usurped an endogenous translation pathway. Together, these findings demonstrate that the ribosome acts as a translational regulator outside of its catalytic role during protein synthesis.