scholarly journals A structured retroviral RNA element that mediates nucleocytoplasmic export of intron-containing RNA.

1997 ◽  
Vol 17 (1) ◽  
pp. 135-144 ◽  
Author(s):  
R K Ernst ◽  
M Bray ◽  
D Rekosh ◽  
M L Hammarskjöld
Keyword(s):  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Regulatory Proteins ◽  
Cellular Factors ◽  
Immunodeficiency Virus ◽  
Rna Export ◽  
Viral Regulatory Proteins ◽  
Responsive Element ◽  
Nucleocytoplasmic Export ◽  
Hiv 1

A common feature of gene expression in all retroviruses is that unspliced, intron-containing RNA is exported to the cytoplasm despite the fact that cellular RNAs which contain introns are usually restricted to the nucleus. In complex retroviruses, the export of intron-containing RNA is mediated by specific viral regulatory proteins (e.g., human immunodeficiency virus type 1 [HIV-1] Rev) that bind to elements in the viral RNA. However, simpler retroviruses do not encode such regulatory proteins. Here we show that the genome of the simpler retrovirus Mason-Pfizer monkey virus (MPMV) contains an element that serves as an autonomous nuclear export signal for intron-containing RNA. This element is essential for MPMV replication; however, its function can be complemented by HIV-1 Rev and the Rev-responsive element. The element can also facilitate the export of cellular intron-containing RNA. These results suggest that the MPMV element mimics cellular RNA transport signals and mediates RNA export through interaction with endogenous cellular factors.

scholarly journals C19ORF66 is an Interferon-Stimulated Gene (ISG) which Inhibits Human Immunodeficiency Virus-1

2016 ◽  
Author(s):  
Weidong Xiong ◽  
Deisy Contreras ◽  
Joseph Ignatius Irudayam ◽  
Ayub Ali ◽  
Otto O. Yang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Nuclear Export ◽  
Splice Variants ◽  
Nuclear Export Signal ◽  
Full Length ◽  
Type I ◽  
Immune Factor ◽  
Immunodeficiency Virus ◽  
P24 Protein ◽  
Hiv 1

ABSTRACTInnate immunity is the first line of defense against invading microbes1. The type I interferon (IFN) pathway plays a key role in controlling Human Immunodeficiency Virus type 1 (HIV-1) replication2,3. We identified an IFN-α stimulated gene C19ORF66 that we term Suppressor of Viral Activity (SVA). Full length SVA-1 protein inhibits HIV-1 by blocking virion production. SVA splice variants truncated at the C-terminus and/or disrupted at the nuclear export signal (NES) lose antiviral activity and localize to nucleus, while full length SVA-1 co-localizes with HIV-1 p24 protein in the cytoplasmic compartment of infected cells. SVA-1 is structurally and functionally conserved across species, including mouse and chimpanzee. We provide the first description of the effector function of the gene SVA/C190RF66 as an innate immune factor with anti-HIV-1 activity.

scholarly journals Concerted Action of Multiple cis-Acting Sequences Is Required for Rev Dependence of Late Human Immunodeficiency Virus Type 1 Gene Expression

2000 ◽  
Vol 74 (22) ◽  
pp. 10822-10826 ◽  
Author(s):  
Marcus Graf ◽  
Alexandra Bojak ◽  
Ludwig Deml ◽  
Kurt Bieler ◽  
Hans Wolf ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nuclear Export ◽  
Regulatory Elements ◽  
Cis Acting ◽  
Immunodeficiency Virus ◽  
Responsive Element ◽  
Hiv 1

ABSTRACT Based on the human immunodeficiency virus type 1 (HIV-1)gag gene, subgenomic reporter constructs have been established allowing the contributions of differentcis-acting elements to the Rev dependency of late HIV-1 gene products to be determined. Modification of intragenic regulatory elements achieved by adapting the codon usage of the complete gene to highly expressed mammalian genes resulted in constitutive nuclear export allowing high levels of Gag expression independent from the Rev/Rev-responsive element system and irrespective of the absence or presence of the isolated major splice donor. Leptomycin B inhibitor studies revealed that the RNAs derived from the codon-optimizedgag gene lacking AU-rich inhibitory elements are directed to a distinct, CRM1-independent, nuclear export pathway.

scholarly journals Adenovirus Late Gene Expression Does Not Require a Rev-Like Nuclear RNA Export Pathway

2000 ◽  
Vol 74 (14) ◽  
pp. 6684-6688 ◽  
Author(s):  
Claudia Rabino ◽  
Anders Aspegren ◽  
Kara Corbin-Lickfett ◽  
Eileen Bridge
Keyword(s):  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Late Gene Expression ◽  
Export Pathway ◽  
Early Proteins ◽  
Immunodeficiency Virus ◽  
Rna Export ◽  
Nuclear Rna Export ◽  
Export Signal

ABSTRACT Adenovirus late mRNA export is facilitated by viral early proteins of 55 and 34 kDa. The 34-kDa protein contains a leucine-rich nuclear export signal (NES) similar to that of the human immunodeficiency virus Rev protein. It was proposed that the 34-kDa protein might facilitate the export of adenovirus late mRNA through a Rev-like NES-mediated export pathway. We have tested the role of NES-mediated RNA export during adenovirus infection, and we find that it is not essential for the expression of adenovirus late genes.

scholarly journals Inhibition of Human Immunodeficiency Virus Rev and Human T-Cell Leukemia Virus Rex Function, but Not Mason-Pfizer Monkey Virus Constitutive Transport Element Activity, by a Mutant Human Nucleoporin Targeted to Crm1

1998 ◽  
Vol 72 (11) ◽  
pp. 8627-8635 ◽  
Author(s):  
Hal P. Bogerd ◽  
Asier Echarri ◽  
Ted M. Ross ◽  
Bryan R. Cullen
Keyword(s):  
Nuclear Export ◽  
Leukemia Virus ◽  
Constitutive Transport Element ◽  
Human T Cell ◽  
Immunodeficiency Virus ◽  
Nuclear Rna ◽  
T Cell Leukemia Virus ◽  
Rna Export ◽  
Nuclear Rna Export ◽  
Hiv 1

ABSTRACT The hypothesis that the cellular protein Crm1 mediates human immunodeficiency virus type 1 (HIV-1) Rev-dependent nuclear export posits that Crm1 can directly interact both with the Rev nuclear export signal (NES) and with cellular nucleoporins. Here, we demonstrate that Crm1 is indeed able to interact with active but not defective forms of the HIV-1 Rev NES and of NESs found in other retroviral nuclear export factors. In addition, we demonstrate that Crm1 can bind the Rev NES when Rev is assembled onto the Rev response element RNA target and that Crm1, like Rev, is a nucleocytoplasmic shuttle protein. Crm1 also specifically binds the Rev NES in vitro, although this latter interaction is detectable only in the presence of added Ran · GTP. Overexpression of a truncated, defective form of the nucleoporin Nup214/CAN, termed ΔCAN, that retains Crm1 binding ability resulted in the effective inhibition of HIV-1 Rev or human T-cell leukemia virus Rex-dependent gene expression. In contrast, ΔCAN had no significant affect on Mason-Pfizer monkey virus constitutive transport element (MPMV CTE)-dependent nuclear RNA export or on the expression of RNAs dependent on the cellular mRNA export pathway. As a result, ΔCAN specifically blocked late, but not early, HIV-1 gene expression in HIV-1-infected cells. These data strongly validate Crm1 as a cellular cofactor for HIV-1 Rev and demonstrate that the MPMV CTE nuclear RNA export pathway uses a distinct, Crm1-independent mechanism. In addition, these data identify a novel and highly potent inhibitor of leucine-rich NES-dependent nuclear export.

scholarly journals Nucleoporins Nup98 and Nup214 Participate in Nuclear Export of Human Immunodeficiency Virus Type 1 Rev

1999 ◽  
Vol 73 (1) ◽  
pp. 120-127 ◽  
Author(s):  
Andrei S. Zolotukhin ◽  
Barbara K. Felber
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nuclear Export ◽  
Competitive Inhibition ◽  
Nuclear Export Signal ◽  
Nuclear Pore ◽  
Immunodeficiency Virus ◽  
Nucleocytoplasmic Export

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Rev contains a leucine-rich nuclear export signal that is essential for its nucleocytoplasmic export mediated by hCRM1. We examined the role of selected nucleoporins, which are located in peripheral structures of the nuclear pore complex and are thought to be involved in export, in Rev function in human cells. First, we found that upon actinomycin D treatment, Nup98, but not Nup214 or Nup153, is able to translocate to the cytoplasm of HeLa cells, demonstrating that Nup98 may act as a soluble factor. We further showed that Rev can recruit Nup98 and Nup214, but not Nup153, to the nucleolus. We also found that the isolated FG-containing repeat domains of Nup98 and Nup214, but not those of Nup153, competitively inhibit the Rev/RRE-mediated expression of HIV. Taken together, the recruitment of Nup98 and Nup214 by Rev and the competitive inhibition exhibited by their NP domains demonstrate direct participation of Nup98 and Nup214 in the Rev-hCRM1-mediated export.

scholarly journals cORF and RcRE, the Rev/Rex and RRE/RxRE Homologues of the Human Endogenous Retrovirus Family HTDV/HERV-K

1999 ◽  
Vol 73 (11) ◽  
pp. 9496-9507 ◽  
Author(s):  
Christine Magin ◽  
Roswitha Löwer ◽  
Johannes Löwer
Keyword(s):  
Nuclear Export ◽  
Leukemia Virus ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Human T Cell ◽  
Immunodeficiency Virus ◽  
T Cell Leukemia Virus ◽  
Import And Export ◽  
Viral Regulatory Proteins ◽  
Responsive Element

ABSTRACT cORF, a protein encoded by the human endogenous retrovirus family HTDV/HERV-K, contains amino acid motifs which resemble the nuclear import and export signals of the viral regulatory proteins Rev (human immunodeficiency virus) and Rex (human T-cell leukemia virus [HTLV]). In this study, we demonstrated that cORF indeed has a Rev-like function and mapped the cORF-responsive RNA element to a sequence in the 3′ long terminal repeat, a localization similar to RxRE, the responsive element in HTLV type 1. Accordingly, we have given the element the designation RcRE. cORF and RcRE stabilize unspliced and incompletely spliced viral transcripts and enhance their nuclear export via the CRM1 export pathway. So far, HTDV/HERV-K is the only endogenous retrovirus family with a complex regulation at the posttranscriptional level. It may be regarded as an intermediate in the evolution from simple to complex retroviruses.

Rev and the fate of pre-mRNA in the nucleus: implications for the regulation of RNA processing in eukaryotes

1993 ◽  
Vol 13 (10) ◽  
pp. 6180-6189 ◽  
Author(s):  
M H Malim ◽  
B R Cullen
Keyword(s):  
T Cells ◽  
Regulation Of Gene Expression ◽  
Nucleocytoplasmic Transport ◽  
Viral Mrnas ◽  
Nuclear Retention ◽  
Human T Cells ◽  
Cellular Factors ◽  
Immunodeficiency Virus ◽  
Nuclear Degradation ◽  
Hiv 1

Although a great deal is known about the regulation of gene expression in terms of transcription, relatively little is known about the modulation of pre-mRNA processing. In this study, we exploited a genetically regulated system, human immunodeficiency virus type 1 (HIV-1) and its trans-activator Rev, to examine events that occur between the synthesis of pre-mRNA in the nucleus and the translation of mRNA in the cytoplasm. Unlike the majority of eukaryotic pre-mRNAs whose introns are efficiently recognized and spliced prior to nucleocytoplasmic transport, HIV-1 mRNAs containing functional introns must be exported to the cytoplasm for the expression of many viral proteins. Using human T cells containing stably integrated proviruses, we demonstrate that such incompletely spliced viral mRNAs are exported to the cytoplasm only in the presence of the Rev trans-activator. In the absence of Rev, these intron-containing RNAs are sequestered in the T-cell nucleus and either spliced or, more commonly, degraded. Because Rev does not inhibit the expression of fully spliced viral mRNA species in T cells, we propose that Rev, rather than inhibiting viral pre-mRNA splicing, is acting here both to prevent the nuclear degradation of HIV-1 pre-mRNAs and to induce their translocation to the cytoplasm. Taken together, these findings indicate that the cellular factors responsible for the nuclear retention of unspliced pre-mRNAs, although most probably splicing factors, do not invariably commit these RNAs to productive splicing and can, instead, program such transcripts for degradation.

An RNA-export mediator with an essential nuclear export signal

Nature ◽  
1996 ◽  
Vol 383 (6598) ◽  
pp. 357-360 ◽  
Author(s):  
Robert Murphy ◽  
Susan R. Wente
Keyword(s):  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Rna Export ◽  
Export Signal
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