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Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei

Every type of nucleic acid in cells undergoes programmed chemical post-transcriptional modification. Generally, modification enzymes use substrates derived from intracellular metabolism, one exception is queuine (q)/queuosine (Q), which eukaryotes obtain from their environment; made by bacteria and...

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Autores principales: Dixit, Sameer, Kessler, Alan C, Henderson, Jeremy, Pan, Xiaobei, Zhao, Ruoxia, D’Almeida, Gabriel Silveira, Kulkarni, Sneha, Rubio, Mary Anne T, Hegedűsová, Eva, Ross, Robert L, Limbach, Patrick A, Green, Brian D, Paris, Zdeněk, Alfonzo, Juan D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682783/
https://www.ncbi.nlm.nih.gov/pubmed/34883512
http://dx.doi.org/10.1093/nar/gkab1204
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author Dixit, Sameer
Kessler, Alan C
Henderson, Jeremy
Pan, Xiaobei
Zhao, Ruoxia
D’Almeida, Gabriel Silveira
Kulkarni, Sneha
Rubio, Mary Anne T
Hegedűsová, Eva
Ross, Robert L
Limbach, Patrick A
Green, Brian D
Paris, Zdeněk
Alfonzo, Juan D
author_facet Dixit, Sameer
Kessler, Alan C
Henderson, Jeremy
Pan, Xiaobei
Zhao, Ruoxia
D’Almeida, Gabriel Silveira
Kulkarni, Sneha
Rubio, Mary Anne T
Hegedűsová, Eva
Ross, Robert L
Limbach, Patrick A
Green, Brian D
Paris, Zdeněk
Alfonzo, Juan D
author_sort Dixit, Sameer
collection PubMed
description Every type of nucleic acid in cells undergoes programmed chemical post-transcriptional modification. Generally, modification enzymes use substrates derived from intracellular metabolism, one exception is queuine (q)/queuosine (Q), which eukaryotes obtain from their environment; made by bacteria and ultimately taken into eukaryotic cells via currently unknown transport systems. Here, we use a combination of molecular, cell biology and biophysical approaches to show that in Trypanosoma brucei tRNA Q levels change dynamically in response to concentration variations of a sub-set of amino acids in the growth media. Most significant were variations in tyrosine, which at low levels lead to increased Q content for all the natural tRNAs substrates of tRNA-guanine transglycosylase (TGT). Such increase results from longer nuclear dwell time aided by retrograde transport following cytoplasmic splicing. In turn high tyrosine levels lead to rapid decrease in Q content. Importantly, the dynamic changes in Q content of tRNAs have negligible effects on global translation or growth rate but, at least, in the case of tRNA(Tyr) it affected codon choice. These observations have implications for the occurrence of other tunable modifications important for ‘normal’ growth, while connecting the intracellular localization of modification enzymes, metabolites and tRNAs to codon selection and implicitly translational output.
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spelling pubmed-86827832021-12-20 Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei Dixit, Sameer Kessler, Alan C Henderson, Jeremy Pan, Xiaobei Zhao, Ruoxia D’Almeida, Gabriel Silveira Kulkarni, Sneha Rubio, Mary Anne T Hegedűsová, Eva Ross, Robert L Limbach, Patrick A Green, Brian D Paris, Zdeněk Alfonzo, Juan D Nucleic Acids Res Molecular Biology Every type of nucleic acid in cells undergoes programmed chemical post-transcriptional modification. Generally, modification enzymes use substrates derived from intracellular metabolism, one exception is queuine (q)/queuosine (Q), which eukaryotes obtain from their environment; made by bacteria and ultimately taken into eukaryotic cells via currently unknown transport systems. Here, we use a combination of molecular, cell biology and biophysical approaches to show that in Trypanosoma brucei tRNA Q levels change dynamically in response to concentration variations of a sub-set of amino acids in the growth media. Most significant were variations in tyrosine, which at low levels lead to increased Q content for all the natural tRNAs substrates of tRNA-guanine transglycosylase (TGT). Such increase results from longer nuclear dwell time aided by retrograde transport following cytoplasmic splicing. In turn high tyrosine levels lead to rapid decrease in Q content. Importantly, the dynamic changes in Q content of tRNAs have negligible effects on global translation or growth rate but, at least, in the case of tRNA(Tyr) it affected codon choice. These observations have implications for the occurrence of other tunable modifications important for ‘normal’ growth, while connecting the intracellular localization of modification enzymes, metabolites and tRNAs to codon selection and implicitly translational output. Oxford University Press 2021-12-09 /pmc/articles/PMC8682783/ /pubmed/34883512 http://dx.doi.org/10.1093/nar/gkab1204 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Molecular Biology
Dixit, Sameer
Kessler, Alan C
Henderson, Jeremy
Pan, Xiaobei
Zhao, Ruoxia
D’Almeida, Gabriel Silveira
Kulkarni, Sneha
Rubio, Mary Anne T
Hegedűsová, Eva
Ross, Robert L
Limbach, Patrick A
Green, Brian D
Paris, Zdeněk
Alfonzo, Juan D
Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei
title Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei
title_full Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei
title_fullStr Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei
title_full_unstemmed Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei
title_short Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei
title_sort dynamic queuosine changes in trna couple nutrient levels to codon choice in trypanosoma brucei
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682783/
https://www.ncbi.nlm.nih.gov/pubmed/34883512
http://dx.doi.org/10.1093/nar/gkab1204
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