A critical step for mRNA expression is the transport from the nucleus to the cytoplasm. Until recently, little information has been available about this important cellular mechanism. While the factors responsible for cellular mRNA transport have not been identified, analysis of retroviral systems have shed light into some important aspects of nuclear mRNA export. HIV mRNA export requires the specific interaction of viral Rev protein with the viral RNA recognition signal, the Rev Responsive Element (RRE), while the type D retrovirus mRNA export is regulated by the cellular TAP/NXF1 protein that interacts with the viral CTE RNA element. While the Rev export requires the cellular receptor CRM1, TAP/NXF1 provides a direct link between mRNA and the nuclear pore complex. These studies are important for the understanding of basic cellular pathways that are also involved in viral regulation and carcinogenesis.We have shown that a major mRNA transport mechanism is conserved in eukaryotes (Tan W, et al: RNA in press). We demonstrated that C elegans encodes a protein, Ce-TAP-1, that is essential for mRNA export and shares molecular features with TAP (Bear J, et al: Mol Cell Biol 19:6306-17, 1999). Therefore, Ce-TAP-1, together with TAP and the yeast Mex67p, belongs to a family of factors that provides a direct molecular link between mRNAs and components of the nuclear pore complex.The identification of hTAP as CTE RNA export factor was a key discovery that led us to better understanding of proteins necessary for the nuclear export of cellular mRNAs. Our data also indicate that the type D retrovirus CTE has evolved to become a high affinity binding site for hTAP, which is necessary to facilitate the export of its unspliced mRNA.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010334-01
Application #
6419959
Study Section
(LGD)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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