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Monitoring the 5’UTR landscape reveals 5’terminal oligopyrimidine (TOP) motif switches to drive translational efficiencies

Ramona Weber, Umesh Ghoshdastider, Daniel Spies, Clara Duré, Fabiola Valdivia-Francia, Merima Forny, Mark Ormiston, Peter F. Renz, David Taborsky, Merve Yigit, Homare Yamahachi, Ataman Sendoel
doi: https://doi.org/10.1101/2021.07.02.450886
Ramona Weber
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
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Umesh Ghoshdastider
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
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Daniel Spies
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
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Clara Duré
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
2Life Science Zurich Graduate School, Molecular Life Science Program, University of Zurich/ ETH Zurich, Switzerland
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Fabiola Valdivia-Francia
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
2Life Science Zurich Graduate School, Molecular Life Science Program, University of Zurich/ ETH Zurich, Switzerland
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Merima Forny
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
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Mark Ormiston
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
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Peter F. Renz
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
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David Taborsky
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
2Life Science Zurich Graduate School, Molecular Life Science Program, University of Zurich/ ETH Zurich, Switzerland
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Merve Yigit
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
2Life Science Zurich Graduate School, Molecular Life Science Program, University of Zurich/ ETH Zurich, Switzerland
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Homare Yamahachi
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
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Ataman Sendoel
1Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, CH-8952 Schlieren-Zurich, Switzerland
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  • For correspondence: ataman.sendoel@uzh.ch
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Abstract

Transcriptional and translational control are key determinants of gene expression, however, to what extent these two processes can be collectively coordinated is still poorly understood. Here we use long-read sequencing to document the 5’and 3’untranslated region (UTR) isoform landscape of epidermal stem cells, wild-type keratinocytes and squamous cell carcinomas. Focusing on squamous cell carcinomas, we show that a small cohort of genes with alternative 5’UTR isoforms exhibit overall increased translational efficiencies and are enriched in ribosomal proteins and splicing factors. These 5’UTR isoforms with identical coding sequences either include or exclude 5’terminal oligopyrimidine (TOP) motifs and result in vastly altered translational efficiencies of the mRNA. Our findings suggest that switching between TOP and non-TOP motif-containing 5’UTR isoforms is an elegant and simple way to alter protein synthesis rates, set their sensitivity to the mTORC1-dependent nutrient-sensing pathway and direct the translational potential of an mRNA by the precise 5’UTR sequence.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 03, 2021.
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Monitoring the 5’UTR landscape reveals 5’terminal oligopyrimidine (TOP) motif switches to drive translational efficiencies
Ramona Weber, Umesh Ghoshdastider, Daniel Spies, Clara Duré, Fabiola Valdivia-Francia, Merima Forny, Mark Ormiston, Peter F. Renz, David Taborsky, Merve Yigit, Homare Yamahachi, Ataman Sendoel
bioRxiv 2021.07.02.450886; doi: https://doi.org/10.1101/2021.07.02.450886
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Monitoring the 5’UTR landscape reveals 5’terminal oligopyrimidine (TOP) motif switches to drive translational efficiencies
Ramona Weber, Umesh Ghoshdastider, Daniel Spies, Clara Duré, Fabiola Valdivia-Francia, Merima Forny, Mark Ormiston, Peter F. Renz, David Taborsky, Merve Yigit, Homare Yamahachi, Ataman Sendoel
bioRxiv 2021.07.02.450886; doi: https://doi.org/10.1101/2021.07.02.450886

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