Codon adaptation to tRNAs with Inosine modification at position 34 is widespread among Eukaryotes and present in two Bacterial phyla

Rafels-Ybern, Àlbert; Torres, Adrián Gabriel; Grau‐Bové, Xavier; Ruiz‐Trillo, Iñaki; Pouplana, Lluı́s Ribas de

doi:10.1080/15476286.2017.1358348

Cited by 57 publications

(57 citation statements)

References 32 publications

(54 reference statements)

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“…In multicellular organisms, A to I editing has been observed in both messenger RNA (mRNA) and tRNA. In bacteria however, only one editing site was discovered in tRNA Arg2 , but never in mRNA (Rafels-Ybern, Torres, Grau-Bove, Ruiz-Trillo, & Ribas de Pouplana, 2018). I generated in the tRNA anticodon is known to pair with U, C, or A in mRNA during translation.…”

Section: Discussionmentioning

confidence: 99%

Expanding targeting scope, editing window, and base transition capability of base editing in Corynebacterium glutamicum

Wang

Liu

et al. 2019

Biotech & Bioengineering

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CRISPR/Cas9‐guided cytidine deaminase enables C:G to T:A base editing in bacterial genome without introduction of lethal double‐stranded DNA break, supplement of foreign DNA template, or dependence on inefficient homologous recombination. However, limited by genome‐targeting scope, editing window, and base transition capability, the application of base editing in metabolic engineering has not been explored. Herein, four Cas9 variants accepting different protospacer adjacent motif (PAM) sequences were used to increase the genome‐targeting scope of bacterial base editing. After a comprehensive evaluation, we demonstrated that PAM requirement of bacterial base editing can be relaxed from NGG to NG using the Cas9 variants, providing 3.9‐fold more target loci for gene inactivation in Corynebacterium glutamicum. Truncated or extended guide RNAs were employed to expand the canonical 5‐bp editing window to 7‐bp. Bacterial adenine base editing was also achieved with Cas9 fused to adenosine deaminase. With these updates, base editing can serve as an enabling tool for fast metabolic engineering. To demonstrate its potential, base editing was used to deregulate feedback inhibition of aspartokinase via amino acid substitution for lysine overproduction. Finally, a user‐friendly online tool named gBIG was provided for designing guide RNAs for base editing‐mediated inactivation of given genes in any given sequenced genome (http://www.ibiodesign.net/gBIG).

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Section: Discussionmentioning

confidence: 99%

Expanding targeting scope, editing window, and base transition capability of base editing in Corynebacterium glutamicum

Wang

Liu

et al. 2019

Biotech & Bioengineering

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“…Complementation of codons and anticodons could be achieved through tRNA modification, with adenosine at the wobble position of the tRNA being converted to inosine. Rafels-Ybern et al. (2017) recently showed that the deamination of this adenosine is widespread amongst eukaryotes and that codons complementary to deaminated tRNA molecules are enriched in highly expressed genes.…”

Section: Discussionmentioning

confidence: 99%

“…The wide-scale deamination of adenosine to inosine is common across different RNA types in Metazoa ( Porath et al. 2017 ) and Rafels-Ybern et al. (2017) showed that metazoan and plant genomes possess a greater concentration of codons translated by modified tRNAs than the genomes of unicellular eukaryotes.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Ancestral Animal Codon Usage Bias Revealed through Holozoan Protists

Southworth

Armitage

Fallon

et al. 2018

Molecular Biology and Evolution

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Choanoflagellates and filastereans are the closest known single celled relatives of Metazoa within Holozoa and provide insight into how animals evolved from their unicellular ancestors. Codon usage bias has been extensively studied in metazoans, with both natural selection and mutation pressure playing important roles in different species. The disparate nature of metazoan codon usage patterns prevents the reconstruction of ancestral traits. However, traits conserved across holozoan protists highlight characteristics in the unicellular ancestors of Metazoa. Presented here are the patterns of codon usage in the choanoflagellates Monosiga brevicollis and Salpingoeca rosetta, as well as the filasterean Capsaspora owczarzaki. Codon usage is shown to be remarkably conserved. Highly biased genes preferentially use GC-ending codons, however there is limited evidence this is driven by local mutation pressure. The analyses presented provide strong evidence that natural selection, for both translational accuracy and efficiency, dominates codon usage bias in holozoan protists. In particular, the signature of selection for translational accuracy can be detected even in the most weakly biased genes. Biased codon usage is shown to have coevolved with the tRNA species, with optimal codons showing complementary binding to the highest copy number tRNA genes. Furthermore, tRNA modification is shown to be a common feature for amino acids with higher levels of degeneracy and highly biased genes show a strong preference for using modified tRNAs in translation. The translationally optimal codons defined here will be of benefit to future transgenics work in holozoan protists, as their use should maximise protein yields from edited transgenes.

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“…We previously suggested that ADAT might be controlling specific genetic programs [45]. Therefore, the BRCA1-driven negative regulation of ADAT2 may silence specific genetic programs the codon usage of which makes their translation dependent on tRNAs with I34 [46]. Emerging evidence indicates that tRNA expression and tRNA repertoire are modulated during tumorigenesis [47,48].…”

Section: Discussionmentioning

confidence: 99%

Uncovering the Translational Regulatory Activity of the Tumor Suppressor BRCA1

Berthel

Vincent

Eberst

et al. 2020

Cells

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BRCA1 inactivation is a hallmark of familial breast cancer, often associated with aggressive triple negative breast cancers. BRCA1 is a tumor suppressor with known functions in DNA repair, transcription regulation, cell cycle control, and apoptosis. In the present study, we demonstrate that BRCA1 is also a translational regulator. We previously showed that BRCA1 was implicated in translation regulation. Here, we asked whether translational control could be a novel function of BRCA1 that contributes to its tumor suppressive activity. A combination of RNA-binding protein immunoprecipitation, microarray analysis, and polysome profiling, was used to identify the mRNAs that were specifically deregulated under BRCA1 deficiency. Western blot analysis allowed us to confirm at the protein level the deregulated translation of a subset of mRNAs. A unique and dedicated cohort of patients with documented germ-line BRCA1 pathogenic variant statues was set up, and tissue microarrays with the biopsies of these patients were constructed and analyzed by immunohistochemistry for their content in each candidate protein. Here, we show that BRCA1 translationally regulates a subset of mRNAs with which it associates. These mRNAs code for proteins involved in major programs in cancer. Accordingly, the level of these key proteins is correlated with BRCA1 status in breast cancer cell lines and in patient breast tumors. ADAT2, one of these key proteins, is proposed as a predictive biomarker of efficacy of treatments recently recommended to patients with BRCA1 deficiency. This study proposes that translational control may represent a novel molecular mechanism with potential clinical impact through which BRCA1 is a tumor suppressor.

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Codon adaptation to tRNAs with Inosine modification at position 34 is widespread among Eukaryotes and present in two Bacterial phyla

Cited by 57 publications

References 32 publications

Expanding targeting scope, editing window, and base transition capability of base editing in Corynebacterium glutamicum

Expanding targeting scope, editing window, and base transition capability of base editing in Corynebacterium glutamicum

Patterns of Ancestral Animal Codon Usage Bias Revealed through Holozoan Protists

Uncovering the Translational Regulatory Activity of the Tumor Suppressor BRCA1

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