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mRNA 降解的温度适应的决定因素。

Determinants of the temperature adaptation of mRNA degradation.

机构信息

Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.

出版信息

Nucleic Acids Res. 2022 Jan 25;50(2):1092-1110. doi: 10.1093/nar/gkab1261.

Abstract

The rate of chemical reactions increases proportionally with temperature, but the interplay of biochemical reactions permits deviations from this relation and adaptation. The degradation of individual mRNAs in yeast increased to varying degrees with temperature. We examined how these variations are influenced by the translation and codon composition of mRNAs. We developed a method that revealed the existence of a neutral half-life above which mRNAs are stabilized by translation but below which they are destabilized. The proportion of these two mRNA subpopulations remained relatively constant under different conditions, even with slow cell growth due to nutrient limitation, but heat shock reduced the proportion of translationally stabilized mRNAs. At the same time, the degradation of these mRNAs was partially temperature-compensated through Upf1, the mediator of nonsense-mediated decay. Compensation was also promoted by some asparagine and serine codons, whereas tyrosine codons promote temperature sensitization. These codons play an important role in the degradation of mRNAs encoding key cell membrane and cell wall proteins, which promote cell integrity.

摘要

化学反应的速率与温度成正比,但生化反应的相互作用允许偏离这种关系和适应。酵母中单个 mRNA 的降解程度随温度的变化而不同。我们研究了这些变化如何受到 mRNA 的翻译和密码子组成的影响。我们开发了一种方法,揭示了存在一个中性半衰期,高于这个半衰期,mRNA 会被翻译稳定,但低于这个半衰期,mRNA 会被不稳定。在不同的条件下,这两种 mRNA 亚群的比例相对保持不变,即使由于营养限制导致细胞生长缓慢,但热休克会降低翻译稳定的 mRNA 的比例。与此同时,通过无意义介导的降解的中介 Upf1,这些 mRNA 的降解部分得到了温度补偿。一些天冬酰胺和丝氨酸密码子也促进了补偿,而酪氨酸密码子则促进了温度敏感性。这些密码子在降解编码关键细胞膜和细胞壁蛋白的 mRNA 中起着重要作用,这些蛋白促进细胞完整性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0be/8789057/aeb30f1f8a0f/gkab1261fig1.jpg

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