去耦降解和平移可实现多(A)尾噪音调制。

Carmen Grandi, Martin Emmaneel, Frank H T Nelissen, Laura W M Roosenboom, Yoanna Petrova, Omnia Elzokla, Maike M K Hansen
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引用次数: 0

摘要

多聚(A)尾对 mRNA 的翻译和降解至关重要,但尾长与 mRNA 动力学之间的确切关系仍不清楚。在这里,我们利用一个小型的相同 mRNA 文库,研究了它们在人类胚胎肾细胞中的行为。我们发现,尾部长度与 mRNA 降解率密切相关,但与翻译无关。有趣的是,最佳尾长度为 100 nt 的翻译率最高,这与纳米孔测序法测得的平均内源尾长度相同。此外,poly(A)-尾长度的可变性--内源性mRNA的特征--影响翻译效率,但不影响mRNA降解率。随机建模结合单细胞追踪发现,poly(A)尾通过将mRNA降解与翻译解耦,为细胞提供了调节基因表达波动的独立控制手段。总之,这项工作有助于对基因表达调控的基本理解,并有可能应用于核酸治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Decoupled degradation and translation enables noise modulation by poly(A) tails.

Decoupled degradation and translation enables noise modulation by poly(A) tails.

Poly(A) tails are crucial for mRNA translation and degradation, but the exact relationship between tail length and mRNA kinetics remains unclear. Here, we employ a small library of identical mRNAs that differ only in their poly(A)-tail length to examine their behavior in human embryonic kidney cells. We find that tail length strongly correlates with mRNA degradation rates but is decoupled from translation. Interestingly, an optimal tail length of ∼100 nt displays the highest translation rate, which is identical to the average endogenous tail length measured by nanopore sequencing. Furthermore, poly(A)-tail length variability-a feature of endogenous mRNAs-impacts translation efficiency but not mRNA degradation rates. Stochastic modeling combined with single-cell tracking reveals that poly(A) tails provide cells with an independent handle to tune gene expression fluctuations by decoupling mRNA degradation and translation. Together, this work contributes to the basic understanding of gene expression regulation and has potential applications in nucleic acid therapeutics.

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