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Analysis at single-cell resolution identifies a stable mammalian tRNA-mRNA interface and increased translation efficiency in neurons

bioRxiv, ISSN: 2692-8205
2021
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Article Description

The correlation between codon and anticodon pools influences the efficiency of translation, but whether differences exist in these pools across individual cells is unknown. We determined that codon usage and amino acid demand are highly stable across different cell types using single-cell RNA-sequencing atlases of adult mouse and fetal human. After demonstrating the robustness of ATAC-sequencing for analysis of tRNA gene usage, we quantified anticodon usage and amino acid supply in adult mouse and fetal human single-cell ATAC-seq atlases. We found that tRNA gene usage is overall coordinated across cell types, except in neurons which clustered separately from other cell types. Integration of these datasets revealed a strong and statistically significant correlation between amino acid supply and demand across almost all cell types. Neurons have an enhanced translation efficiency over other cell types, driven by an increased supply of tRNA (AGC) anticodons. This results in faster decoding of the Ala-GCC codon, as determined by cell-type specific ribosome profiling, and a reduction of tRNA (AGC) anticodon pools may be implicated in neurological pathologies. This study, the first such examination of codon usage, anticodon usage, and translation efficiency at single-cell resolution, identifies conserved features of translation elongation across mammalian cellular diversity and evolution.

Bibliographic Details

William Gao; Carlos J. Gallardo-Dodd; Claudia Kutter

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

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