Quantifying the effect of ribosomal density on mRNA stability.

Quantifying the effect of ribosomal density on mRNA stability.
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DOI:
10.1371/journal.pone.0102308
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Tuller T
Tuller T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Edri S;Tuller T

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基因表达是一个基本的细胞过程,通过该过程,蛋白质最终基于基因中编码的信息合成。该过程包括四个主要步骤:对应于基因的DNA片段转录为mRNA分子,mRNA分子的降解,mRNA分子通过核糖体翻译为蛋白质以及蛋白质的降解。我们提出了一个创新的定量研究之间的相互作用的基因翻译阶段和mRNA降解阶段使用大规模的基因组数据的S。酿酒酵母,包括mRNA水平,mRNA半衰期,核糖体密度和蛋白质丰度的测量,为数千个基因。报道的结果支持的推测,转录与较高的核糖体密度,这是相关的翻译阶段,往往有升高的半衰期,我们提出了一种新的定量估计这种关系的强度。具体来说,我们表明,平均而言,核糖体密度增加78%,mRNA半衰期增加25%,核糖体密度和mRNA半衰期之间的这种关系是不特定的功能。此外,我们的分析表明,核糖体密度沿着整个ORF,而不是在特定的位置,有一个显着的影响转录半衰期。最后,我们表明,不能用基因间的不同表达水平来解释所报道的关系。对报告结果的一个合理解释是,核糖体倾向于保护mRNA分子免受外泌体复合物的降解;然而,本文讨论了对报告关系的其他非互斥的可能解释及其验证实验。
Gene expression is a fundamental cellular process by which proteins are eventually synthesized based on the information coded in the genes. This process includes four major steps: transcription of the DNA segment corresponding to a gene to mRNA molecules, the degradation of the mRNA molecules, the translation of mRNA molecules to proteins by the ribosome and the degradation of the proteins. We present an innovative quantitative study of the interaction between the gene translation stage and the mRNA degradation stage using large scale genomic data of S. cerevisiae, which include measurements of mRNA levels, mRNA half-lives, ribosomal densities and protein abundances, for thousands of genes. The reported results support the conjecture that transcripts with higher ribosomal density, which is related to the translation stage, tend to have elevated half-lives, and we suggest a novel quantitative estimation of the strength of this relation. Specifically, we show that on average, an increase of 78% in ribosomal density yields an increase of 25% in mRNA half-life, and that this relation between ribosomal density and mRNA half-life is not function specific. In addition, our analyses demonstrate that ribosomal density along the entire ORF, and not in specific locations, has a significant effect on the transcript half-life. Finally, we show that the reported relation cannot be explained by different expression levels among genes. A plausible explanation for the reported results is that ribosomes tend to protect the mRNA molecules from the exosome complexes degrading them; however, additional non-mutually exclusive possible explanations for the reported relation and experiments for their verifications are discussed in the paper.
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