Nuclear mRNA export: insights from virology

doi:10.1016/S0968-0004(03)00142-7

Trends in Biochemical Sciences

Volume 28, Issue 8, August 2003, Pages 419-424

https://doi.org/10.1016/S0968-0004(03)00142-7 Get rights and content

Abstract

To maximize the production of progeny virions, several viruses have evolved mechanisms that promote the selective nuclear export of viral mRNA transcripts while, in some cases, inhibiting the export of cellular mRNAs. To achieve this goal, viruses have evolved regulatory proteins and cis-acting RNA elements that selectively interact with key cellular nuclear export factors. Efforts to identify the cellular targets of these viral proteins and RNA elements have led to the identification of Crm1 and Tap as essential human nuclear RNA-export factors and continue to provide insights into how mRNAs are selected for export

Section snippets

The HIV-1 Rev protein

Although the genome packaged into retroviral virions is a single-stranded mRNA, the retroviral replication cycle proceeds via a double-stranded DNA derivative, termed a provirus, that is integrated into the host genome [3]. The pathogenic retrovirus human immunodeficiency virus type 1 (HIV-1) has a total of nine genes that are expressed by alternative splicing of a single, initial proviral transcript that also forms the RNA genome. Importantly, HIV-1 replication requires the nuclear export and

The retroviral constitutive transport element

HIV-1 is a complex retrovirus; HIV-1 encodes not only the canonical structural proteins (Gag and Env) and enzymes (Pol) required for the retroviral life cycle but also additional auxiliary and regulatory proteins, including Rev (Fig. 1). By contrast, simple retroviruses, such as Mason–Pfizer monkey virus (MPMV), encode only Gag, Pol and Env [3]. Yet MPMV also encodes both an unspliced RNA that serves as the genome and as the Gag and Pol mRNA, as well as a spliced mRNA encoding Env. The same

Nuclear export of herpesvirus mRNAs

The fact that the retroviral life cycle requires the nuclear export of intron-containing viral RNAs, in the face of cellular proofreading mechanisms that seek to prevent the expression of cellular pre-mRNAs, means that retroviruses have been the most informative viral system in which to study nuclear mRNA export. However, other viruses have also evolved mechanisms to selectively promote the nuclear export of their mRNAs. One interesting example of this occurs in herpes simplex virus (HSV).

ICP27

Other viruses, other export pathways

Although the viral nuclear mRNA-export systems discussed here are the most fully developed, study of other viruses has also shed light on nuclear mRNA export or has, at least, raised unresolved issues that have the potential to lead the mRNA-export field in new directions. Among retroviruses, it is clear that the majority of complex retroviruses, including all lentiviruses and members of the T-cell leukemia retrovirus family, encode Rev homologs [3]. An interesting Rev homolog was found in the

Concluding remarks

Virology has made several key contributions to our current understanding of how mRNAs are exported from the nucleus. Study of the HIV-1 replication cycle led to the identification of Rev as the first nuclear mRNA-export factor, enabled the definition of the most common form of NES and identified Crm1 as the cellular target for Rev NES function (Fig. 2). Analysis of MPMV CTE function has led to the identification of Tap as a crucial factor in the nuclear export of cellular mRNAs and, in

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Trends in Biochemical Sciences

Nuclear mRNA export: insights from virology

Abstract

Section snippets

The HIV-1 Rev protein

The retroviral constitutive transport element

Nuclear export of herpesvirus mRNAs

Other viruses, other export pathways

Concluding remarks

Cell

Trends Cell Biol.

Virology

Cell

Cell

Cell

Cell

Cell

Curr. Biol.

Mol. Cell

Curr. Biol.

Mol. Cell

Curr. Biol.

Curr. Biol.

Mol. Cell

J. Biol. Chem.

Mol. Cell

A second post-transcriptional trans-activator gene required for HTLV-III replication

Nature

The HIV-1 Rev transactivator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA

Nature

Nuclear export of different classes of RNA is mediated by specific factors

J. Cell Biol.

Nuclear RNA export

J. Cell Sci.

Genome-wide analysis of nuclear mRNA export pathways in Drosophila

EMBO J.

Protein ligands to HuR modulate its interaction with target mRNAs in vivo

J. Cell Biol.

A small element from the Mason–Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent

Proc. Natl. Acad. Sci. U. S. A.