Differential translation elongation directs protein synthesis in response to acute glucose deprivation in yeast.
Differential translation elongation directs protein synthesis in response to acute glucose deprivation in yeast.
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DOI：
10.1080/15476286.2022.2065784
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发表时间：
2022
期刊：
影响因子：
4.1
通讯作者：
Zid, Brian M.
中科院分区：
文献类型：
--
作者：
Guzikowski, Anna R.;Harvey, Alex T.;Zhang, Jingxiao;Zhu, Shihui;Begovich, Kyle;Cohn, Molly H.;Wilhelm, James E.;Zid, Brian M.
关键词：
蛋白质的合成在能量上是昂贵的，并且其速率受到诸如细胞类型和环境等因素的影响。翻译抑制是细胞环境中应激变化的典型反应。特别是，翻译起始步骤的抑制已被强调为应激诱导的翻译抑制中的关键控制步骤，因为快速抑制起始的机制是保守的。然而，细胞已经进化出复杂的调控手段来控制除了起始之外的翻译。在这里，我们研究的作用，翻译的延伸步骤在酵母进行急性葡萄糖剥夺。核糖体分析和体内报告基因测定的使用表明，在葡萄糖去除后，延伸速率逐渐减慢。我们观察到，核糖体分布广泛转移到转录的下游末端后，急性和渐进的葡萄糖剥夺，但不响应于其他压力。此外，在评估的mRNA，核糖体占用和蛋白质生产压力前之间存在的相关性，但压力后丢失。这些结果表明，应激诱导的伸长调节导致核糖体减慢并在响应葡萄糖戒断的转录组的相当大的比例上积累。最后，我们报告核糖体建立了沿着成绩单有能力恢复延长和完成蛋白质合成后，再添加葡萄糖饥饿的细胞。这表明酵母已经进化出响应于葡萄糖饥饿而减缓翻译延伸的机制，这并不妨碍从这些核糖体继续产生蛋白质，从而避免了需要新的起始事件来合成蛋白质。缩略语：八月：起始密码子，bp：碱基对，CDS：编码序列，CHX：放线菌酮，eEF 2：真核延伸因子2，LTM：乳酰亚胺霉素，nt：核苷酸，PGK 1：3-磷酸甘油酸激酶，核糖体生物发生：ribi，RO：核糖体占有率，RPF：核糖体保护片段，TE：翻译效率
Protein synthesis is energetically expensive and its rate is influenced by factors such as cell type and environment. Suppression of translation is a canonical response to stressful changes in the cellular environment. In particular, inhibition of the initiation step of translation has been highlighted as the key control step in stress-induced translational suppression as mechanisms that quickly suppress initiation are well-conserved. However, cells have evolved complex regulatory means to control translation apart from initiation. Here, we examine the role of the elongation step of translation in yeast subjected to acute glucose deprivation. The use of ribosome profiling and in vivo reporter assays demonstrated elongation rates slow progressively following glucose removal. We observed that ribosome distribution broadly shifts towards the downstream ends of transcripts after both acute and gradual glucose deprivation but not in response to other stressors. Additionally, on assessed mRNAs, a correlation existed between ribosome occupancy and protein production pre-stress but was lost after stress. These results indicate that stress-induced elongation regulation causes ribosomes to slow down and build up on a considerable proportion of the transcriptome in response to glucose withdrawal. Finally, we report ribosomes that built up along transcripts are competent to resume elongation and complete protein synthesis after readdition of glucose to starved cells. This suggests that yeast has evolved mechanisms to slow translation elongation in response to glucose starvation which do not preclude continuation of protein production from those ribosomes, thereby averting a need for new initiation events to take place to synthesize proteins. Abbreviations: AUG: start codon, bp: base pair(s), CDS: coding sequence, CHX: cycloheximide, eEF2: eukaryotic elongation factor 2, LTM: lactimidomycin, nt: nucleotide, PGK1: 3-phosphoglycerate kinase, ribosomal biogenesis: ribi, RO: ribosome occupancy, RPF: ribosome protected fragment, TE: translational efficiency
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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DOI：
10.1083/jcb.201806183
发表时间：
2018-12-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Khong A;Parker R
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影响因子：
12.3
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Costello JL;Kershaw CJ;Castelli LM;Talavera D;Rowe W;Sims PFG;Ashe MP;Grant CM;Hubbard SJ;Pavitt GD
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Pavitt GD