MLV requires Tap/NXF1-dependent pathway to export its unspliced RNA to the cytoplasm and to express both spliced and unspliced RNAs
Open accessAbstract
BACKGROUND: Eukaryotic cells have evolved stringent proofreading mechanisms to ensure that intron-containing mRNAs do not leave the nucleus. However, all retroviruses must bypass this checkpoint for replication. Indeed, their primary polycistronic transcript (Full-Length) must reach the cytoplasm to be either translated or packaged as genomic RNA in progeny viruses.Murine leukemia virus (MLV) is a prototype of simple retroviruses with only two well-regulated splicing events that directly influence viral leukemogenic properties in mice. Several cis-elements have been identified in the FL RNA that regulate its cytoplasmic accumulation. However, their connection with an export mechanism is yet unknown. Our goal was to identify the cellular pathway used by MLV to export its RNAs into the cytoplasm of the host cells. RESULTS: Since other retroviruses use the CRM1 and/or the Tap/NXF1 pathways to export their unspliced RNA from the nucleus, we investigated the role of these two pathways in MLV replication by using specific inhibitors. The effects of export inhibition on MLV protein synthesis, RNA levels and RNA localization were studied by Western blotting, RT-qPCR, fluorescence microscopy and ribonucleoprotein immunoprecipitation assays. Taken together, our results show for the first time that MLV requires the Tap/NXF1-mediated export pathway, and not the CRM1 pathway, for the expression of its spliced and unspliced RNAs and for FL RNA nuclear export. CONCLUSIONS: By contrast to HIV-1, MLV recruits the same pathway for the cytoplasmic expression of its spliced and unspliced RNAs. Thus, MLV RNA expression depends upon coordinated splicing/export processes. In addition, FL RNA translation relies on Tap/NXF1-dependent export, raising the critical question of whether the pool of FL RNA to be packaged is also exported by Tap/NXF1.
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In MLV, a cytoplasmic accumulation element has been identified in the pol gene that interacts with NXF1 to export unspliced and spliced RNA transcripts from the nucleus to the cytoplasm.
“A similar mechanism has also been observed in MLV, where a cytoplasmic accumulation element has been identified in the pol gene that interacts with NXF1 to export unspliced and spliced RNA transcripts from the nucleus to the cytoplasm (Fig. 9) (Pessel-Vivares et al. 2014, Sakuma et al. 2014).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Pessel-Vivares et al. 2014
The Abstract (Results) and Findings report that MLV uses the Tap/NXF1 pathway for unspliced RNA nuclear export and for expression of both spliced and unspliced RNAs. But the paper does not identify a cytoplasmic accumulation element in the pol gene or show that such an element interacts with NXF1; the Findings describe known accumulation-related elements in the 5′ UTR and leave their connection to export unresolved. No page numbers are available in our copy. (LLM, conf=0.88)
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- Authors
- Pessel-Vivares, L., Ferrer, M., Lainé, S., & Mougel, M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Lainé, Sébastien
- Mougel, Marylène
- Venue
- Retrovirology
- Published
- 2014-03-05
- Volume
- 11
- Issue
- 1
- Pages
- 21-21
- ISSN
- 1742-4690 (ISSN-L)
- PMC
- PMC4015919
- OpenAlex
- W2133204833
- Cited by
- 19
- References
- 27
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 1 · 2020: 5 · 2019: 1 · 2018: 2 · 2016: 3 · 2015: 2 · 2014: 2
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Retrovirology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de Recherches sur le Sida et les Hépatites Virales
- Ligue Contre le Cancer
- Ministère de l'Enseignement Supérieur et de la Recherche
- Centre National de la Recherche Scientifique
- CHIST-ERA
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- murine leukemia virus, nuclear export, unspliced RNA, viral RNA translation, viral RNA packaging
- MeSH terms
- Animals, Antigens, Ly, Cell Line, Cytoplasm, Membrane Proteins, Leukemia Virus, Murine, RNA, Messenger, RNA, Viral, Viral Proteins, Blotting, Western, Gene Expression, Reverse Transcriptase Polymerase Chain Reaction, Active Transport, Cell Nucleus, Nucleocytoplasmic Transport Proteins, Mice, Real-Time Polymerase Chain Reaction
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