Université de Toulouse; INSA, UPS, INP; LISBP, 135 Avenue de Rangueil, F-31077, Toulouse, France.
BMC Genomics. 2013 Aug 28;14:588. doi: 10.1186/1471-2164-14-588.
The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation.
A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation.To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although mRNA stabilization and lower dilution by growth counterbalanced this effect.
We show that the contribution of translational regulation to the control of gene expression is significant in the stress response. Post-transcriptional regulation is complex and not systematically co-directional with transcription regulation. Post-transcriptional regulation is important to the understanding of gene expression control.
细菌的应激反应涉及基因表达的多阶段控制，但尚未完全理解。为了确定应激条件下细菌的翻译反应，并评估其对基因表达调控的贡献，我们比较了在最佳生长条件下和营养（异亮氨酸）饥饿时所有 mRNA 的翻译状态。
在模式细菌乳球菌中进行了营养限制的翻译反应的全基因组研究。使用两种措施来评估每个个体 mRNA 的翻译状态：参与翻译的部分（核糖体占有率）和核糖体密度（每 100 个核苷酸的核糖体数）。在异亮氨酸饥饿时，一半的 mRNA 被翻译下调，主要是由于核糖体密度降低。这种模式涉及与生长相关的功能，如翻译、转录和脂肪酸、磷脂和碱基的代谢有关的基因，导致生长速度减慢。只有 4%的 mRNA 被翻译上调，主要与应激时的噬菌表达有关。其余基因表现出两种翻译标志物的拮抗调节。尽管核糖体密度降低，但所有参与异亮氨酸生物合成的基因的核糖体占有率都显著增加。结果揭示了该途径复杂的翻译调控，这对于应对异亮氨酸饥饿至关重要。
为了更普遍地阐明全局基因表达的调控，我们比较了异亮氨酸饥饿时的转录调控和与 mRNA 降解和生长引起的 mRNA 稀释相关的其他转录后调控的翻译调控。尽管 mRNA 稳定和生长引起的稀释作用抵消了这种效应，但翻译调控似乎加剧了转录变化对异亮氨酸饥饿下生长相关功能下调的影响。
我们表明，在应激反应中，翻译调控对基因表达调控的贡献是显著的。转录后调控复杂，与转录调控不完全同向。转录后调控对于理解基因表达调控很重要。
