Abstract

The genetic code is an abstraction of how mRNA codons and tRNA anticodons molecularly interact during protein synthesis; the stability and regulation of this interaction remains largely unexplored. Here, we characterized the expression of mRNA and tRNA genes quantitatively at multiple time points in two developing mouse tissues. We discovered that mRNA codon pools are highly stable over development and simply reflect the genomic background; in contrast, precise regulation of tRNA gene families is required to create the corresponding tRNA transcriptomes. The dynamic regulation of tRNA genes during development is controlled in order to generate an anticodon pool that closely corresponds to messenger RNAs. Thus, across development, the pools of mRNA codons and tRNA anticodons are invariant and highly correlated, revealing a stable molecular interaction interlocking transcription and translation.

Highlights

  • Transcription of the mammalian genome is divided among multiple RNA polymerases (Pol), each transcribing a nonoverlapping set of genes

  • If the large-scale changes in protein-coding transcriptomes result in a stable distribution of Messenger RNAs (mRNAs) triplet codons, deliberate changes in the population of transfer RNAs (tRNAs) anticodons could be used to fine-tune protein translation

  • We found a high correlation between these two pools, revealing that this key tRNA–mRNA interface is actively stabilized across mammalian development

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Summary

Introduction

Transcription of the mammalian genome is divided among multiple RNA polymerases (Pol), each transcribing a nonoverlapping set of genes. We dissected the interdependencies of transcriptional and translational components in matched liver and whole brain tissue samples taken from C57BL/6J mice at eight developmental stages (from E9.5 to P29) on a genome-wide level by using RNA-sequencing (RNA-seq) and Pol III chromatin immunoprecipitation followed by sequencing (ChIP-seq) to quantify mRNA and tRNA gene expression levels, respectively (Fig. 1).

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