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A Chemical Kinetic Basis for Measuring Translation Initiation and Elongation Rates from Ribosome Profiling data

ABSTRACT: A Chemical Kinetic Basis for Measuring Translation Initiation and Elongation Rates from Ribosome Profiling data

PROVIDER: PRJNA478925 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7464190.fastq.gz	Fastqsanger.gz
	SRR7464191.fastq.gz	Fastqsanger.gz
	SRR7464192.fastq.gz	Fastqsanger.gz
	SRR7464193.fastq.gz	Fastqsanger.gz
	SRR7464188.fastq.gz	Fastqsanger.gz

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A Chemical Kinetic Basis for Measuring Translation Initiation and Elongation Rates from Ribosome Profiling data

Project description:Analysis methods based on simulations and optimization have been previously developed to estimate relative translation rates from next-generation sequencing data. Translation involves molecules and chemical reactions; hence, bioinformatics methods consistent with the laws of chemistry and physics are more likely to produce accurate results. Here, we derive simple equations based on chemical kinetic principles to measure the translation-initiation rate, transcriptome-wide elongation rate, and individual codon translation rates from ribosome profiling experiments. Our methods reproduce the known rates from ribosome profiles generated from detailed simulations of translation. Applying our methods to data from S. cerevisiae and mouse embryonic stem cells we find that the extracted rates reproduce previously reported correlations with various molecular quantities. A codon can exhibit up to 26-fold variability in its translation rate depending upon its context with in a transcript. This broad distribution means that the average translation rate of a codon is not representative of the rate at which most instances of that codon are translated. We also find that mouse embryonic stem cells have a global translation speed that is almost two-fold faster than previously reported. This large variability in translation rates suggests that translational regulation might be used by cells to a greater degree than previously thought.

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A chemical kinetic basis for measuring translation initiation and elongation rates from ribosome profiling data.

Project description:Analysis methods based on simulations and optimization have been previously developed to estimate relative translation rates from next-generation sequencing data. Translation involves molecules and chemical reactions, hence bioinformatics methods consistent with the laws of chemistry and physics are more likely to produce accurate results. Here, we derive simple equations based on chemical kinetic principles to measure the translation-initiation rate, transcriptome-wide elongation rate, and individual codon translation rates from ribosome profiling experiments. Our methods reproduce the known rates from ribosome profiles generated from detailed simulations of translation. By applying our methods to data from S. cerevisiae and mouse embryonic stem cells, we find that the extracted rates reproduce expected correlations with various molecular properties, and we also find that mouse embryonic stem cells have a global translation speed of 5.2 AA/s, in agreement with previous reports that used other approaches. Our analysis further reveals that a codon can exhibit up to 26-fold variability in its translation rate depending upon its context within a transcript. This broad distribution means that the average translation rate of a codon is not representative of the rate at which most instances of that codon are translated, and it suggests that translational regulation might be used by cells to a greater degree than previously thought.

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