Interplay between the alpharetroviral Gag protein and SR proteins SF2 and SC35 in the nucleus

Breanna L. Rice, Rebecca J. Kaddis, Matthew S. Stake, Timothy L. Lochmann, Leslie J. Parent

Research output: Contribution to journalArticle

  • 2 Citations

Abstract

Retroviruses are positive-sense, single-stranded RNA viruses that reverse transcribe their RNA genomes into double-stranded DNA for integration into the host cell chromosome. The integrated provirus is used as a template for the transcription of viral RNA. The full-length viral RNA can be used for the translation of the Gag and Gag-Pol structural proteins or as the genomic RNA (gRNA) for encapsidation into new virions by the Gag protein. The mechanism by which Gag selectively incorporates unspliced gRNA into virus particles is poorly understood. Although Gag was previously thought to localize exclusively to the cytoplasm and plasma membrane where particles are released, we found that the Gag protein of Rous sarcoma virus, an alpharetrovirus, undergoes transient nuclear trafficking. When the nuclear export signal of RSV Gag is mutated (Gag. L219A), the protein accumulates in discrete subnuclear foci reminiscent of nuclear bodies such as splicing speckles, paraspeckles, and PML bodies. In this report, we observed that RSV Gag. L219A foci appeared to be tethered in the nucleus, partially co-localizing with the splicing speckle components SC35 and SF2. Overexpression of SC35 increased the number of Gag. L219A nucleoplasmic foci, suggesting that SC35 may facilitate the formation of Gag foci. We previously reported that RSV Gag nuclear trafficking is required for efficient gRNA packaging. Together with the data presented herein, our findings raise the intriguing hypothesis that RSV Gag may co-opt splicing factors to localize near transcription sites. Because splicing occurs co-transcriptionally, we speculate that this mechanism could allow Gag to associate with unspliced viral RNA shortly after its transcription initiation in the nucleus, before the viral RNA can be spliced or exported from the nucleus as an mRNA template.

LanguageEnglish (US)
Article number00925
JournalFrontiers in Microbiology
Volume6
Issue numberSEP
DOIs
StatePublished - Jan 1 2015

Fingerprint

gag Gene Products
Viral RNA
RNA Viruses
RNA
Virion
gag-pol Fusion Proteins
Proteins
Alpharetrovirus
Nuclear Export Signals
Rous sarcoma virus
Proviruses
Product Packaging
Retroviridae
Cytoplasm
Chromosomes
Cell Membrane
Genome
Messenger RNA
DNA

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Microbiology (medical)

Cite this

Rice, Breanna L. ; Kaddis, Rebecca J. ; Stake, Matthew S. ; Lochmann, Timothy L. ; Parent, Leslie J./ Interplay between the alpharetroviral Gag protein and SR proteins SF2 and SC35 in the nucleus. In: Frontiers in Microbiology. 2015 ; Vol. 6, No. SEP.
@article{d0d887804acf44cbba71f3b7bf61e7c9,
title = "Interplay between the alpharetroviral Gag protein and SR proteins SF2 and SC35 in the nucleus",
abstract = "Retroviruses are positive-sense, single-stranded RNA viruses that reverse transcribe their RNA genomes into double-stranded DNA for integration into the host cell chromosome. The integrated provirus is used as a template for the transcription of viral RNA. The full-length viral RNA can be used for the translation of the Gag and Gag-Pol structural proteins or as the genomic RNA (gRNA) for encapsidation into new virions by the Gag protein. The mechanism by which Gag selectively incorporates unspliced gRNA into virus particles is poorly understood. Although Gag was previously thought to localize exclusively to the cytoplasm and plasma membrane where particles are released, we found that the Gag protein of Rous sarcoma virus, an alpharetrovirus, undergoes transient nuclear trafficking. When the nuclear export signal of RSV Gag is mutated (Gag. L219A), the protein accumulates in discrete subnuclear foci reminiscent of nuclear bodies such as splicing speckles, paraspeckles, and PML bodies. In this report, we observed that RSV Gag. L219A foci appeared to be tethered in the nucleus, partially co-localizing with the splicing speckle components SC35 and SF2. Overexpression of SC35 increased the number of Gag. L219A nucleoplasmic foci, suggesting that SC35 may facilitate the formation of Gag foci. We previously reported that RSV Gag nuclear trafficking is required for efficient gRNA packaging. Together with the data presented herein, our findings raise the intriguing hypothesis that RSV Gag may co-opt splicing factors to localize near transcription sites. Because splicing occurs co-transcriptionally, we speculate that this mechanism could allow Gag to associate with unspliced viral RNA shortly after its transcription initiation in the nucleus, before the viral RNA can be spliced or exported from the nucleus as an mRNA template.",
author = "Rice, {Breanna L.} and Kaddis, {Rebecca J.} and Stake, {Matthew S.} and Lochmann, {Timothy L.} and Parent, {Leslie J.}",
year = "2015",
month = "1",
day = "1",
doi = "10.3389/fmicb.2015.00925",
language = "English (US)",
volume = "6",
journal = "Frontiers in Microbiology",
issn = "1664-302X",
publisher = "Frontiers Media S. A.",
number = "SEP",

}

Interplay between the alpharetroviral Gag protein and SR proteins SF2 and SC35 in the nucleus. / Rice, Breanna L.; Kaddis, Rebecca J.; Stake, Matthew S.; Lochmann, Timothy L.; Parent, Leslie J.

In: Frontiers in Microbiology, Vol. 6, No. SEP, 00925, 01.01.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interplay between the alpharetroviral Gag protein and SR proteins SF2 and SC35 in the nucleus

AU - Rice,Breanna L.

AU - Kaddis,Rebecca J.

AU - Stake,Matthew S.

AU - Lochmann,Timothy L.

AU - Parent,Leslie J.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Retroviruses are positive-sense, single-stranded RNA viruses that reverse transcribe their RNA genomes into double-stranded DNA for integration into the host cell chromosome. The integrated provirus is used as a template for the transcription of viral RNA. The full-length viral RNA can be used for the translation of the Gag and Gag-Pol structural proteins or as the genomic RNA (gRNA) for encapsidation into new virions by the Gag protein. The mechanism by which Gag selectively incorporates unspliced gRNA into virus particles is poorly understood. Although Gag was previously thought to localize exclusively to the cytoplasm and plasma membrane where particles are released, we found that the Gag protein of Rous sarcoma virus, an alpharetrovirus, undergoes transient nuclear trafficking. When the nuclear export signal of RSV Gag is mutated (Gag. L219A), the protein accumulates in discrete subnuclear foci reminiscent of nuclear bodies such as splicing speckles, paraspeckles, and PML bodies. In this report, we observed that RSV Gag. L219A foci appeared to be tethered in the nucleus, partially co-localizing with the splicing speckle components SC35 and SF2. Overexpression of SC35 increased the number of Gag. L219A nucleoplasmic foci, suggesting that SC35 may facilitate the formation of Gag foci. We previously reported that RSV Gag nuclear trafficking is required for efficient gRNA packaging. Together with the data presented herein, our findings raise the intriguing hypothesis that RSV Gag may co-opt splicing factors to localize near transcription sites. Because splicing occurs co-transcriptionally, we speculate that this mechanism could allow Gag to associate with unspliced viral RNA shortly after its transcription initiation in the nucleus, before the viral RNA can be spliced or exported from the nucleus as an mRNA template.

AB - Retroviruses are positive-sense, single-stranded RNA viruses that reverse transcribe their RNA genomes into double-stranded DNA for integration into the host cell chromosome. The integrated provirus is used as a template for the transcription of viral RNA. The full-length viral RNA can be used for the translation of the Gag and Gag-Pol structural proteins or as the genomic RNA (gRNA) for encapsidation into new virions by the Gag protein. The mechanism by which Gag selectively incorporates unspliced gRNA into virus particles is poorly understood. Although Gag was previously thought to localize exclusively to the cytoplasm and plasma membrane where particles are released, we found that the Gag protein of Rous sarcoma virus, an alpharetrovirus, undergoes transient nuclear trafficking. When the nuclear export signal of RSV Gag is mutated (Gag. L219A), the protein accumulates in discrete subnuclear foci reminiscent of nuclear bodies such as splicing speckles, paraspeckles, and PML bodies. In this report, we observed that RSV Gag. L219A foci appeared to be tethered in the nucleus, partially co-localizing with the splicing speckle components SC35 and SF2. Overexpression of SC35 increased the number of Gag. L219A nucleoplasmic foci, suggesting that SC35 may facilitate the formation of Gag foci. We previously reported that RSV Gag nuclear trafficking is required for efficient gRNA packaging. Together with the data presented herein, our findings raise the intriguing hypothesis that RSV Gag may co-opt splicing factors to localize near transcription sites. Because splicing occurs co-transcriptionally, we speculate that this mechanism could allow Gag to associate with unspliced viral RNA shortly after its transcription initiation in the nucleus, before the viral RNA can be spliced or exported from the nucleus as an mRNA template.

UR - http://www.scopus.com/inward/record.url?scp=84949671544&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949671544&partnerID=8YFLogxK

U2 - 10.3389/fmicb.2015.00925

DO - 10.3389/fmicb.2015.00925

M3 - Article

VL - 6

JO - Frontiers in Microbiology

T2 - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

IS - SEP

M1 - 00925

ER -