Murine leukemia virus uses NXF1 for nuclear export of spliced and unspliced viral transcripts

Toshie Sakuma, Jaime I. Davila, Jessica A. Malcolm, Jean-Pierre Kocher, Jason M. Tonne, Yasuhiro H Ikeda

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Intron-containing mRNAs are subject to restricted nuclear export in higher eukaryotes. Retroviral replication requires the nucleocytoplasmic transport of both spliced and unspliced RNA transcripts, and RNA export mechanisms of gammaretroviruses are poorly characterized. Here, we report the involvement of the nuclear export receptor NXF1/TAP in the nuclear export of gammaretroviral RNA transcripts. We identified a conserved cis-acting element in the pol gene of gammaretroviruses, including murine leukemia virus (MLV) and xenotropic murine leukemia virus (XMRV), named the CAE (cytoplasmic accumulation element). The CAE enhanced the cytoplasmic accumulation of viral RNA transcripts and the expression of viral proteins without significantly affecting the stability, splicing, or translation efficiency of the transcripts. Insertion of the CAE sequence also facilitated Rev-independent HIV Gag expression. We found that the CAE sequence interacted with NXF1, whereas disruption of NXF1 ablated CAE function. Thus, the CAE sequence mediates the cytoplasmic accumulation of gammaretroviral transcripts in an NXF1-dependent manner. Disruption of NXF1 expression impaired cytoplasmic accumulations of both spliced and unspliced RNA transcripts of XMRV and MLV, resulting in their nuclear retention or degradation. Thus, our results demonstrate that gammaretroviruses use NXF1 for the cytoplasmic accumulation of both spliced and nonspliced viral RNA transcripts.

Original languageEnglish (US)
Pages (from-to)4069-4082
Number of pages14
JournalJournal of Virology
Volume88
Issue number8
DOIs
StatePublished - 2014

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Murine leukemia virus
Murine Leukemia Viruses
Cell Nucleus Active Transport
Gammaretrovirus
messenger RNA
RNA
Viral RNA
pol Genes
nucleocytoplasmic transport
Viral Proteins
Cytoplasmic and Nuclear Receptors
Eukaryota
Introns
viral proteins
translation (genetics)
HIV
eukaryotic cells
introns
Messenger RNA
receptors

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Murine leukemia virus uses NXF1 for nuclear export of spliced and unspliced viral transcripts. / Sakuma, Toshie; Davila, Jaime I.; Malcolm, Jessica A.; Kocher, Jean-Pierre; Tonne, Jason M.; Ikeda, Yasuhiro H.

In: Journal of Virology, Vol. 88, No. 8, 2014, p. 4069-4082.

Research output: Contribution to journalArticle

Sakuma, Toshie ; Davila, Jaime I. ; Malcolm, Jessica A. ; Kocher, Jean-Pierre ; Tonne, Jason M. ; Ikeda, Yasuhiro H. / Murine leukemia virus uses NXF1 for nuclear export of spliced and unspliced viral transcripts. In: Journal of Virology. 2014 ; Vol. 88, No. 8. pp. 4069-4082.
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