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翻译延长作为蛋白质生产的速度限制步骤

Elijah F Lyons¹, Lou C Devanneaux¹, Ryan Y Muller¹

¹Department of Molecular and Cell Biology, University of California, Berkeley, California.

bioRxiv : the preprint server for biology

|December 11, 2023

概括

同义代码子选择直接影响蛋白质的产生,与之前的模型相反. 缓慢的翻译延长减少了每个mRNA的蛋白质输出,揭示了基因表达的动态平衡.

科学领域:

分子生物学分子生物学
合成生物学合成生物学
遗传学是一个遗传学.

背景情况:

同义代码子选择影响基因表达,但它对蛋白质输出的直接影响仍在争论中.
简单的模型表明翻译启动,而不是代码子速度,限制了每个mRNA的蛋白质生产.

研究的目的:

调查同名编码子选择对蛋白质产量的直接影响.
为了确定缓慢的翻译延长是否会影响超出mRNA稳定的蛋白质生产.
探索蛋白质合成中翻译启动和延长之间的相互作用.

主要方法:

使用神经网络模型设计了同名的光蛋白记者.
在酵母中进行了实验,以测量蛋白质产量和mRNA稳定性.
利用全基因组的CRISPR干扰 (CRISPRi) 屏幕来调节翻译启动.
进行模拟以建模翻译动态.

主要成果:

同义代码子选择显著改变了蛋白质输出,在记者中观察到的范围是7倍.
缓慢的翻译延长直接减少了每mRNA产生的蛋白质数量,独立于mRNA稳定性.
削弱翻译启动减少了缓慢延长的负面影响,表明这些步骤之间的平衡.
子的选择可以在子使用变化的自然范围内限制蛋白质的生产.

结论:

同义代码子选择是蛋白质输出的直接决定因素,不仅仅受到翻译启动的影响.
在调节蛋白质合成的翻译延长速度和启动效率之间存在动态相互作用.
这些发现对理解内源基因表达和设计合成mRNA疗法有重要意义.

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