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Journal of Virology, December 2001, p. 11735-11746, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11735-11746.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Retroviruses Human Immunodeficiency Virus Type 1 and Moloney Murine Leukemia Virus Adopt Radically Different Strategies To Regulate Promoter-Proximal Polyadenylation

Andre Furger, Joan Monks, and Nick J. Proudfoot*

Sir William Dunn School of Pathology, Oxford University, Oxford OX1 3RE, United Kingdom

Received 30 April 2001/Accepted 9 August 2001

Maximal gene expression in retroviruses requires that polyadenylation in the 5' long terminal repeat (LTR) is suppressed. In human immunodeficiency virus type 1 (HIV-1) the promoter-proximal poly(A) site is blocked by interaction of U1 snRNP with the closely positioned major splice donor site (MSD) 200 nucleotides downstream. Here we investigated whether the same mechanism applies to down-regulate 5' LTR polyadenylation in Moloney murine leukemia virus (MoMLV). Although the same molecular architecture is present in both viruses, the MoMLV poly(A) signal in the 5' LTR is active whether or not the MSD is mutated. This surprising difference between the two retroviruses is not due to their actual poly(A) signals or MSD sequences, since exchange of either element between the two viral sequences does not alter their ability to regulate 5' LTR poly(A) site use. Instead we demonstrate that sequence between the cap and AAUAAA is required for MSD-dependent poly(A) regulation in HIV-1, indicating a key role for this part of the LTR in poly(A) site suppression. We also show that the MoMLV poly(A) signal is an intrinsically weak RNA-processing signal. This suggests that in the absence of a poly(A) site suppression mechanism, MoMLV is forced to use a weak poly(A) signal.

* Corresponding author. Mailing address: Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford, United Kingdom OX1 3RE. Phone: 44-1865-275566. Fax: 44-1865-275556. E-mail: nicholas.proudfoot{at}path.ox.ac.uk.

Journal of Virology, December 2001, p. 11735-11746, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11735-11746.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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