Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, Zhejiang, China.
Commun Biol. 2022 Sep 1;5(1):892. doi: 10.1038/s42003-022-03853-4.
The chemical modification of ribosomes plays an important regulatory role in cellular translation adaptation in response to environmental stresses. Nevertheless, how the modified ribosome reprograms the translation machinery for the preferential expression of the specific mRNAs encoding stress-responsive proteins to stress remains poorly understood. Here, we find that AcP-induced acetylation of K411 and K464 in ribosomal protein S1 during carbon-nitrogen imbalance, which in turn impacts its binding with distinct mRNAs. S1 acetylation shows differential selectivity for recruiting subsets of mRNAs to ribosomes. Using the RNC-Seq method, we find that mimic acetylated S1 prefers transcripts related with the formation of flagella/biofilms, two-component systems, nitrogen assimilation, amino acid degradation, and lipopolysaccharide biosynthesis, whereas inhibits the translation of mRNAs involved in amino acid biosynthesis and most ribosomal proteins. Importantly, further characterization of S1-binding site (SBS) sequences of mRNAs with different translation efficiencies indicated that the presence of a conserved motif allows coordinated regulation of S1 acetylation-driven translation reprogramming for cell survival during nitrogen starvation. These findings expand the repertoire of ribosome heterogeneity to the acetylation level of S1 at specific sites and its role in the ribosome-mediated regulation of gene expression as a cellular response at the translational level to stress.
核糖体的化学修饰在细胞翻译适应环境应激中起着重要的调节作用。然而，修饰后的核糖体如何重新编程翻译机制，优先表达编码应激反应蛋白的特定 mRNA，以应对应激，目前还知之甚少。在这里，我们发现碳氮失衡时核糖体蛋白 S1 上的 K411 和 K464 发生 AcP 诱导的乙酰化，进而影响其与不同 mRNA 的结合。S1 乙酰化对核糖体募集特定 mRNA 亚群表现出不同的选择性。利用 RNC-Seq 方法，我们发现模拟乙酰化 S1 优先选择与鞭毛/生物膜形成、双组分系统、氮同化、氨基酸降解和脂多糖生物合成相关的转录本，而抑制与氨基酸生物合成和大多数核糖体蛋白相关的 mRNA 的翻译。重要的是，对翻译效率不同的 mRNA 的 S1 结合位点（SBS）序列的进一步表征表明，保守基序的存在允许协调调节 S1 乙酰化驱动的翻译重编程，以促进氮饥饿期间细胞的存活。这些发现扩展了核糖体异质性的范围，包括特定位点的 S1 乙酰化水平及其在核糖体介导的基因表达调控中的作用，这是细胞在翻译水平上对应激的反应。
