Bi-directional ribosome scanning controls the stringency of start codon selection.
Bi-directional ribosome scanning controls the stringency of start codon selection.
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DOI：
10.1038/s41467-021-26923-3
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发表时间：
2021-11-15
影响因子：
16.6
通讯作者：
Qian SB
中科院分区：
文献类型：
--
作者：
Gu Y;Mao Y;Jia L;Dong L;Qian SB
在蛋白质合成过程中，核糖体对起始密码子识别的保真度是至关重要的。目前对真核生物翻译起始的认识意味着前起始复合物（PIC）沿5 ′ UTR沿着单向5 ′ →3 ′迁移。在探测翻译起始从超短的5 ′ UTR，我们报告说，一个AUG三联体附近的5 ′端可以选择通过PIC回滑。双向核糖体扫描由紧密间隔的AUG密码子的竞争性选择和内部核糖体进入位点侧翼的两个起始位点的识别支持。转录组范围的PIC分析揭示了在5 ′末端和起始密码子附近具有振荡模式的足迹。消耗RNA解旋酶eIF4A导致PIC振荡减少和5个末端起始密码子的选择受损。增强eIF4A的ATP酶活性促进非线性PIC扫描并刺激上游翻译起始。解旋酶介导的PIC构象开关可能提供了一种操作机制，统一核糖体募集，扫描和起始密码子选择。通常认为起始密码子选择通过40 S核糖体对mRNA的单向扫描发生。在这里，作者提供的证据表明，前起始复合物可以在mRNA上反向滑动，以启动上游AUG密码子的翻译。
The fidelity of start codon recognition by ribosomes is paramount during protein synthesis. The current knowledge of eukaryotic translation initiation implies unidirectional 5ʹ→3ʹ migration of the pre-initiation complex (PIC) along the 5ʹ UTR. In probing translation initiation from ultra-short 5ʹ UTR, we report that an AUG triplet near the 5ʹ end can be selected via PIC backsliding. Bi-directional ribosome scanning is supported by competitive selection of closely spaced AUG codons and recognition of two initiation sites flanking an internal ribosome entry site. Transcriptome-wide PIC profiling reveals footprints with an oscillation pattern near the 5ʹ end and start codons. Depleting the RNA helicase eIF4A leads to reduced PIC oscillations and impaired selection of 5ʹ end start codons. Enhancing the ATPase activity of eIF4A promotes nonlinear PIC scanning and stimulates upstream translation initiation. The helicase-mediated PIC conformational switch may provide an operational mechanism that unifies ribosome recruitment, scanning, and start codon selection. Start codon selection is commonly thought to occur through the unidirectional scanning of the mRNA by the 40 S ribosome. Here the authors provide evidence that the pre-initiation complex can backslide on the mRNA to initiate translation at upstream AUG codons.
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