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Journal Article

tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding.

MPS-Authors
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Konevega,  A. L.
Department of Physical Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Mittelstät,  J.
Department of Physical Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Rodnina,  M. V.
Department of Physical Biochemistry, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

1798488.pdf
(Publisher version), 1011KB

Supplementary Material (public)

1798488-Suppl-1.pdf
(Supplementary material), 2MB

1798488-Suppl-2.xls
(Supplementary material), 2MB

Citation

Rezgui, V. A. N., Kshitiz, T., Namit, R., Konevega, A. L., Mittelstät, J., Rodnina, M. V., et al. (2013). tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding. Proceedings of the National Academy of Sciences of the United States of America, 110(30), 12289-12294. doi:10.1073/pnas.1300781110.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0013-F8E3-6
Abstract
tRNA modifications are crucial to ensure translation efficiency and fidelity. In eukaryotes, the URM1 and ELP pathways increase cellular resistance to various stress conditions, such as nutrient starvation and oxidative agents, by promoting thiolation and methoxycarbonylmethylation, respectively, of the wobble uridine of cytoplasmic Formula (tKUUU), Formula (tQUUG), and Formula (tEUUC). Although in vitro experiments have implicated these tRNA modifications in modulating wobbling capacity and translation efficiency, their exact in vivo biological roles remain largely unexplored. Using a combination of quantitative proteomics and codon-specific translation reporters, we find that translation of a specific gene subset enriched for AAA, CAA, and GAA codons is impaired in the absence of URM1- and ELP-dependent tRNA modifications. Moreover, in vitro experiments using native tRNAs demonstrate that both modifications enhance binding of tKUUU to the ribosomal A-site. Taken together, our data suggest that tRNA thiolation and methoxycarbonylmethylation regulate translation of genes with specific codon content.