Abstract
Control of translation is vital to all species. Here we employ a multi-omics approach to decipher condition-dependent translational regulation in the model acetogen Clostridium ljungdahlii. Integration of data from cells grown autotrophically or heterotrophically revealed that pathways critical to carbon and energy metabolism are under strong translational regulation. Major pathways involved in carbon and energy metabolism are not only differentially transcribed and translated, but their translational efficiencies are differentially elevated in response to resource availability under different growth conditions. We show that translational efficiency is not static and that it changes dynamically in response to mRNA expression levels. mRNAs harboring optimized 5′-untranslated region and coding region features, have higher translational efficiencies and are significantly enriched in genes encoding carbon and energy metabolism. In contrast, mRNAs enriched in housekeeping functions harbor sub-optimal features and have lower translational efficiencies. We propose that regulation of translational efficiency is crucial for effectively controlling resource allocation in energy-deprived microorganisms.
Highlights
Control of translation is vital to all species
We find that RAST subsystems belonging to these pathways are significantly enriched in mRNA with optimized 5′-untranslated region (5′UTR) features (i.e. high-affinity ribosomebinding site (RBS), increased AU content upstream of the RBS, and optimal distance of RBS from the translation initiation site) and optimized coding region features (high codon adaptation index (CAI) and low AU content)
We carried out RNA sequencing (RNA-seq) and Ribo-seq experiments for autotrophic cultures of C. ljungdahlii grown either on CO or H2:CO2 and heterotrophic cultures grown on fructose
Summary
Control of translation is vital to all species. Here we employ a multi-omics approach to decipher condition-dependent translational regulation in the model acetogen Clostridium ljungdahlii. MRNAs harboring optimized 5′-untranslated region and coding region features, have higher translational efficiencies and are significantly enriched in genes encoding carbon and energy metabolism. Next-generation omic approaches, such as RNAseq, proteomics, and metabolomics, have been employed to identify the functionality and organizational structure of acetogenic bacterial genomes[8,9,10,11] These approaches directly addressed the genotype −phenotype relationship in bacteria, providing crucial insights into the design strategies for microbial cell factories. Translation is a major energy burden especially for cells growing in nutrient-deficient conditions In these niches optimization of resource allocation becomes increasingly critical for survival. We combined Ribo-seq, RNA-seq, and transcription start site sequencing (TSS-seq) to study how resources are allocated under energy-rich heterotrophic growth and energydeprived autotrophic growth conditions in the model acetogen C. ljungdahlii. We propose that selective control of TE in key metabolic and energy pathways is critical for thriving in nutritionally deprived niches
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