A global characterization of the translational and transcriptional programs induced by methionine restriction through ribosome profiling and RNA-seq

BMC Genomics

Research Article

Hao Li¹  Jiashun Zheng¹  Ke Zou²  Qi Ouyang³ 

[1] Department of Biochemistry and Biophysics, University of California, 94158, San Francisco, CA, USA;The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, 100871, Beijing, China;Department of Biochemistry and Biophysics, University of California, 94158, San Francisco, CA, USA;The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, 100871, Beijing, China;Peking-Tsinghua Center for Life Sciences and Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, 100871, Beijing, China;

关键词: Translational Efficiency;    Translational Regulation;    Lifespan Extension;    Amino Acid Starvation;    Ribosomal Profile;   

DOI  :  10.1186/s12864-017-3483-2

 received in 2016-10-25, accepted in 2017-01-10,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAmong twenty amino acids, methionine has a special role as it is coded by the translation initiation codon and methionyl-tRNAi (Met-tRNAi) is required for the assembly of the translation initiation complex. Thus methionine may play a special role in global gene regulation. Methionine has also been known to play important roles in cell growth, development, cancer, and aging. In this work, we characterize the translational and transcriptional programs induced by methionine restriction (MetR) and investigate the potential mechanisms through which methionine regulates gene expression, using the budding yeast S. cerevisiae as the model organism.ResultsUsing ribosomal profiling and RNA-seq, we observed a broad spectrum of gene expression changes in response to MetR and identified hundreds of genes whose transcript level and/or translational efficiency changed significantly. These genes show clear functional themes, suggesting that cell slows down its growth and cell cycle progression and increases its stress resistance and maintenance in response to MetR. Interestingly, under MetR cell also decreases glycolysis and increases respiration, and increased respiration was linked to lifespan extension caused by caloric restriction. Analysis of genes whose translational efficiency changed significantly under MetR revealed different modes of translational regulation: 1) Ribosome loading patterns in the 5′UTR and coding regions of genes with increased translational efficiency suggested mechanisms both similar and different from that for the translational regulation of Gcn4 under general amino acid starvation condition; 2) Genes with decreased translational efficiency showed strong enrichment of lysine, glutamine, and glutamate codons, supporting the model that methionine can regulate translation by controlling tRNA thiolation.ConclusionsMetR induced a broad spectrum of gene expression changes at both the transcriptional and translational levels, with clear functional themes indicative of the physiological state of the cell under MetR. Different modes of translational regulation were induced by MetR, including the regulation of the ribosome loading at 5′UTR and regulation by tRNA thiolation. Since MetR extends the lifespan of many species, the list of genes we identified in this study can be good candidates for studying the mechanisms of lifespan extension.

【 授权许可】

CC BY   
© The Author(s). 2017

【 图 表 】

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