A picornavirus protein interacts with Ran-GTPase and disrupts nucleocytoplasmic transport
Open accessAbstract
Active nucleocytoplasmic transport of protein and RNA in eukaryotes depends on the Ran-GTPase system to regulate cargo–receptor interactions. Several viruses, including the RNA picornaviruses, encode factors that alter nuclear transport with the aim of suppressing synthesis of antiviral factors and promoting viral replication. Picornaviruses in the cardiovirus genus express a unique 67-aa Leader protein (L), known to alter the subcellular distribution of IFN regulatory proteins targeted to the nucleus. We report here that L binds directly to Ran and blocks nuclear export of new mRNAs. In Xenopus egg extracts, recombinant L also inhibits mitotic spindle assembly, a RanGTP function crucial to cell-cycle progression. We propose that L inhibits nucleocytoplasmic transport during infection by disrupting the RanGDP/GTP gradient. This inhibition triggers an efflux of nuclear proteins necessary for viral replication and causes IFN suppression. To our knowledge, L is the first viral picornaviral protein to interact directly with Ran and modulate the Ran-dependent nucleocytoplasmic pathway.
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EMCV L protein appears to suppress interferon production and impair nucleo-cytoplasmic trafficking through the binding of Ran-GTPase and through phosphorylation and inactivation of nucleoporins.
“Even if EMCV L protein is devoid of any known enzymatic activity, in contrast to that of aphtovirus, it appears to suppress interferon production149 and impair nucleo-cytoplasmic trafficking through the binding of Ran-GTPase (Ras-related nuclear -GTPase required for the RNA and protein translocation through the nuclear pores) and through phosphorylation and inactivation of nucleoporins.150-154”
From The encephalomyocarditis virus (2012) · cites this paper as [154]
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Self-citation
- Authors
- Porter, F. W., Bochkov, Y. A., Albee, A. J., Wiese, C., & Palmenberg, A. C.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-08-15
- Volume
- 103
- Issue
- 33
- Pages
- 12417-12422
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1567894
- OpenAlex
- W2050807285
- Cited by
- 112
- References
- 36
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 2 · 2016: 2 · 2015: 7 · 2014: 8 · 2013: 8 · 2012: 7
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0344723)
- American Heart Association
- National Institutes of Health (AI-17331)
- National Institute of Allergy and Infectious Diseases (AI17331, R56AI017331, R01AI017331)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- picornavirus, cardiovirus, leader protein, Ran GTPase, nuclear transport, nuclear export, interferon inhibition, mitotic spindle assembly, viral replication, antiviral factors, Xenopus egg extracts
- MeSH terms
- Amino Acid Sequence, Animals, HeLa Cells, Humans, Spindle Apparatus, Molecular Sequence Data, Nuclear Envelope, Oocytes, Picornaviridae, Viral Proteins, Xenopus laevis, Sequence Alignment, ran GTP-Binding Protein, Active Transport, Cell Nucleus
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