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- W4225409063 abstract "ABSTRACT Translation is a key determinant of gene expression and an important biotechnological engineering target. In bacteria, 5’-untranslated region (5’-UTR) and coding sequence (CDS) are well-known mRNA parts controlling translation and thus cellular protein levels. However, the complex interaction of 5’-UTR and CDS has so far only been studied for few sequences leading to non-generalisable and partly contradictory conclusions. Herein, we systematically assess the dynamic translation from over 1.2 million 5’-UTR-CDS pairs in Escherichia coli to investigate their collective effect using a new method for ultradeep sequence-function mapping. This allows us to disentangle and precisely quantify effects of known and hypothetical sequence determinants of translation. We find that 5’-UTR and CDS individually account for 53% and 20% of variance in translation, respectively, and show conclusively that, contrary to a common hypothesis, tRNA abundance does not explain expression changes between CDSs with different synonymous codons. Moreover, the obtained large-scale data clearly point to a base-pairing interaction between initiator tRNA and mRNA beyond the anticodon-codon interaction, an effect that is often masked for individual sequences and therefore inaccessible to low-throughput approaches. Our study highlights the indispensability of ultradeep sequence-function mapping to accurately determine the contribution of parts and phenomena involved in gene regulation." @default.
- W4225409063 created "2022-05-05" @default.
- W4225409063 creator A5080880291 @default.
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- W4225409063 date "2022-05-02" @default.
- W4225409063 modified "2023-10-16" @default.
- W4225409063 title "Ultradeep characterisation of translational sequence determinants refutes rare-codon hypothesis and unveils quadruplet base pairing of initiator tRNA and transcript" @default.
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- W4225409063 doi "https://doi.org/10.1101/2022.05.02.490318" @default.
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