Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability.
Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability.
复制标题
DOI：
10.7554/elife.85545
复制
发表时间：
2023-06-02
期刊：
影响因子：
7.7
通讯作者：
Hinnebusch AG
中科院分区：
文献类型：
--
作者：
Vijjamarri AK;Niu X;Vandermeulen MD;Onu C;Zhang F;Qiu H;Gupta N;Gaikwad S;Greenberg ML;Cullen PJ;Lin Z;Hinnebusch AG
大多数酵母mRNA的降解涉及Dcp 1/Dcp 2的脱帽。DEAD盒蛋白Dhh 1被认为是去帽的激活剂，在偶联密码子非最优性增强降解，并作为翻译抑制剂，但其在细胞中的功能还不完全清楚。RNA-Seq分析结合所有加帽mRNA的CAGE测序显示，dcp 2 Δ细胞中数百种mRNA的丰度增加，这似乎直接归因于受损的去帽而不是转录升高。有趣的是，只有一部分mRNA需要Dhh 1才能被Dcp 2靶向，并且通常还需要其他的去帽激活剂Pat 1、Edc 3或Scd 6;而大多数剩余的转录本利用无义介导的mRNA衰变因子来进行Dcp 2介导的周转。无论是低效的翻译起始还是停滞的延伸似乎都不是Dhh 1增强mRNA降解的主要驱动因素。令人惊讶的是，核糖体分析显示dcp 2 Δ赋予相对翻译效率（TE）的广泛变化，这通常有利于良好翻译的mRNA。由于dcp 2 Δ降低了核糖体的生物合成，同时增加了加帽mRNA的丰度，我们认为mRNA与核糖体的比例增加了mRNA之间的竞争，以限制核糖体有利于dcp 2 Δ细胞中有效翻译的mRNA。有趣的是，参与呼吸或利用替代碳或氮源的基因被上调，并且在dcp 2 Δ细胞中线粒体功能和细胞表达都升高，这表明去帽在转录后雕刻基因表达，以根据营养物质的可用性微调代谢途径和形态转变。
Degradation of most yeast mRNAs involves decapping by Dcp1/Dcp2. DEAD-box protein Dhh1 has been implicated as an activator of decapping, in coupling codon non-optimality to enhanced degradation, and as a translational repressor, but its functions in cells are incompletely understood. RNA-Seq analyses coupled with CAGE sequencing of all capped mRNAs revealed increased abundance of hundreds of mRNAs in dcp2Δ cells that appears to result directly from impaired decapping rather than elevated transcription. Interestingly, only a subset of mRNAs requires Dhh1 for targeting by Dcp2, and also generally requires the other decapping activators Pat1, Edc3, or Scd6; whereas most of the remaining transcripts utilize nonsense-mediated mRNA decay factors for Dcp2-mediated turnover. Neither inefficient translation initiation nor stalled elongation appears to be a major driver of Dhh1-enhanced mRNA degradation. Surprisingly, ribosome profiling revealed that dcp2Δ confers widespread changes in relative translational efficiencies (TEs) that generally favor well-translated mRNAs. Because ribosome biogenesis is reduced while capped mRNA abundance is increased by dcp2Δ, we propose that an increased ratio of mRNA to ribosomes increases competition among mRNAs for limiting ribosomes to favor efficiently translated mRNAs in dcp2Δ cells. Interestingly, genes involved in respiration or utilization of alternative carbon or nitrogen sources are upregulated, and both mitochondrial function and cell filamentation are elevated in dcp2Δ cells, suggesting that decapping sculpts gene expression post-transcriptionally to fine-tune metabolic pathways and morphological transitions according to nutrient availability.