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Ribosome assembly defects subvert initiation Factor3 mediated scrutiny of bona fide start signal

机译:核糖体组装缺陷破坏起始因子3介导的真正起始信号的检测

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摘要

In bacteria, the assembly factors tightly orchestrate the maturation of ribosomes whose competency for protein synthesis is validated by translation machinery at various stages of translation cycle. However, what transpires to the quality control measures when the ribosomes are produced with assembly defects remains enigmatic. In , we show that 30S ribosomes that harbour assembly defects due to the lack of assembly factors such as RbfA and KsgA display suboptimal initiation codon recognition and bypass the critical codon–anticodon proofreading steps during translation initiation. These premature ribosomes on entering the translation cycle compromise the fidelity of decoding that gives rise to errors during initiation and elongation. We show that the assembly defects compromise the binding of initiation factor 3 (IF3), which in turn appears to license the rapid transition of 30S (pre) initiation complex to 70S initiation complex by tempering the validation of codon–anticodon interaction during translation initiation. This suggests that the premature ribosomes harbouring the assembly defects subvert the IF3 mediated proofreading of cognate initiation codon to enter the translation cycle.
机译:在细菌中,组装因子紧密协调核糖体的成熟,核糖体的蛋白质合成能力已在翻译循环的各个阶段通过翻译机制验证。然而,当产生具有组装缺陷的核糖体时,对质量控制措施的表现仍然是个谜。在中,我们显示了由于缺少装配因子(如RbfA和KsgA)而具有装配缺陷的30S核糖体显示了次优的起始密码子识别,并在翻译起始过程中绕过了关键的密码子-反密码子校对步骤。这些过早的核糖体在进入翻译循环时会损害解码的保真度,从而在起始和延伸过程中引起错误。我们表明,组装缺陷损害了起始因子3(IF3)的结合,而后者又通过缓和翻译起始过程中密码子-反密码子相互作用的验证,从而使30S(pre)起始复合物迅速过渡到70S起始复合物。这表明具有装配缺陷的过早核糖体破坏了IF3介导的同源起始密码子的校对,从而进入翻译循环。

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