Affiliation:
1. Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712
Abstract
ABSTRACT
Mouse mammary tumor virus (MMTV) has been classified as a simple retrovirus with two accessory genes,
dut
and
sag
. Cloned MMTV proviruses carrying a trimethoprim (
trim
) cassette in the envelope gene were defective for Gag protein production and the nuclear export of unspliced
gag-pol
RNA. Complementation experiments indicated that a
trans
-acting product was responsible for the Gag defect of such mutants. Analysis of MMTV-infected cells revealed the presence of a novel, doubly spliced RNA that encodes a putative product of 301 amino acids. Overexpression of cDNA from this RNA increased Gag levels from
env
mutant proviruses or reporter gene expression from unspliced mRNAs and allowed detection of a 33-kDa protein product, which has been named
r
egulator of
e
xport of MMTV
m
RNA, or Rem. The Rem N terminus has motifs similar to the Rev-like export proteins of complex retroviruses, and mutation of the nuclear localization signal (NLS) abolished RNA export and detection within the nucleus. The Rem C terminus has few identifiable features, but removal of this domain increased Rem-mediated export, suggesting an autoregulatory function. A reporter vector developed from the 3′ end of the MMTV provirus was Rem responsive and required both the presence of the MMTV
env
-U3 junction and a functional Crm1 pathway. The identification of a third accessory protein from a doubly spliced transcript suggests that MMTV is the first murine complex retrovirus to be documented. Manipulation of the MMTV genome may provide mouse models for human retroviral diseases, such as AIDS.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
109 articles.
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