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Dissecting the import and export pathways of the human RNA helicase UPF1

View ORCID ProfileAndrea B. Eberle, Karin Schranz, View ORCID ProfileSofia Nasif, Lena Grollmus, View ORCID ProfileOliver Mühlemann
doi: https://doi.org/10.1101/2021.08.02.454737
Andrea B. Eberle
1Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland
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Karin Schranz
1Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland
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Sofia Nasif
1Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland
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Lena Grollmus
1Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland
2School of Life Sciences, EPFL, Station 19, 1015 Lausanne, Switzerland
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Oliver Mühlemann
1Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland
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  • For correspondence: oliver.muehlemann@dcb.unibe.ch
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Abstract

The RNA helicase UPF1 is best known for its key role in mRNA surveillance but has been implicated in additional cellular processes both in the nucleus and in the cytoplasm. In human cells, the vast majority of UPF1 resides in the cytoplasm and only small amounts can be detected in the nucleus at steady state. It was previously shown that its export from the nucleus to the cytoplasm is Crm1-dependent, yet neither the nuclear export signal (NES) nor the nuclear localization signal (NLS) has been identified. Here, we provide evidence for a noncanonical NLS in UPF1, map the NES to amino acids 89-105 and show that L103 and F105 are essential for UPF1’s export to the cytoplasm. Examination of additional UPF1 mutants revealed that a functional helicase domain but not the association with RNA is crucial for the shuttling capacity of UPF1.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 02, 2021.
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Dissecting the import and export pathways of the human RNA helicase UPF1
Andrea B. Eberle, Karin Schranz, Sofia Nasif, Lena Grollmus, Oliver Mühlemann
bioRxiv 2021.08.02.454737; doi: https://doi.org/10.1101/2021.08.02.454737
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Dissecting the import and export pathways of the human RNA helicase UPF1
Andrea B. Eberle, Karin Schranz, Sofia Nasif, Lena Grollmus, Oliver Mühlemann
bioRxiv 2021.08.02.454737; doi: https://doi.org/10.1101/2021.08.02.454737

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