This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Graveley, B. R. Articles by Gilmartin, G. M. Search for Related Content PubMed PubMed Citation Articles by Graveley, B. R. Articles by Gilmartin, G. M.

 Previous Article  |  Next Article 

J. Virol., Mar 1996, 1612-1617, Vol 70, No. 3
Copyright © 1996, American Society for Microbiology

A common mechanism for the enhancement of mRNA 3' processing by U3 sequences in two distantly related lentiviruses

BR Graveley and GM Gilmartin
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington 05405, USA.

The protein coding regions of all retroviral pre-mRNAs are flanked by a direct repeat of R-U5 sequences. In many retroviruses, the R-U5 repeat contains a complete core poly(A) site-composed of a highly conserved AAUAAA hexamer and a GU-rich downstream element. A mechanism that allows for the bypass of the 5' core poly(A) site and the exclusive use of the 3' core poly(A) site must therefore exist. In human immunodeficiency virus type 1 (HIV-1), sequences within the U3 region appear to play a key role in poly(A) site selection. U3 sequences are required for efficient 3' processing at the HIV-1 poly(A) site both in vivo and in vitro. These sequences serve to promote the interaction of cleavage and polyadenylation specificity factor (CPSF) with the core poly(A) site. We have now demonstrated the presence of a functionally analogous 3' processing enhancer within the U3 region of a distantly related lentivirus, equine infectious anemia virus (EIAV). U3 sequences enhanced the processing of the EIAV core poly(A) site sevenfold in vitro. The U3 sequences also enhanced the stability of CPSF binding at the core poly(A) site. Optimal processing required the TAR RNA secondary structure that resides within the R region 28 nucleotides upstream of the AAUAAA hexamer. Disruption of TAR reduced processing, while compensatory changes that restored the RNA structure also restored processing to the wild-type level, suggesting a position dependence of the U3-encoded enhancer sequences. Finally, the reciprocal exchange of the EIAV and HIV U3 regions demonstrated the ability of each of these sequences to enhance both 3' processing and the binding of CPSF in the context of the heterologous core poly(A) site. The impact of U3 sequences upon the interaction of CPSF at the core poly(A) site may therefore represent a common strategy for retroviral poly(A) site selection.

This article has been cited by other articles:

• Grigoras, I., Timchenko, T., Gronenborn, B. (2008). Transcripts encoding the nanovirus master replication initiator proteins are terminally redundant. J. Gen. Virol. 89: 583-593 [Abstract] [Full Text]  
• Furger, A., Monks, J., Proudfoot, N. J. (2001). The Retroviruses Human Immunodeficiency Virus Type 1 and Moloney Murine Leukemia Virus Adopt Radically Different Strategies To Regulate Promoter-Proximal Polyadenylation. J. Virol. 75: 11735-11746 [Abstract] [Full Text]  
• Rothnie, H. M., Chen, G., Fütterer, J., Hohn, T. (2001). Polyadenylation in Rice Tungro Bacilliform Virus: cis-Acting Signals and Regulation. J. Virol. 75: 4184-4194 [Abstract] [Full Text]  
• Brackenridge, S., Proudfoot, N. J. (2000). Recruitment of a Basal Polyadenylation Factor by the Upstream Sequence Element of the Human Lamin B2 Polyadenylation Signal. Mol. Cell. Biol. 20: 2660-2669 [Abstract] [Full Text]  
• Hans, H., Alwine, J. C. (2000). Functionally Significant Secondary Structure of the Simian Virus 40 Late Polyadenylation Signal. Mol. Cell. Biol. 20: 2926-2932 [Abstract] [Full Text]  
• Chao, L. C., Jamil, A., Kim, S. J., Huang, L., Martinson, H. G. (1999). Assembly of the Cleavage and Polyadenylation Apparatus Requires About 10 Seconds In Vivo and Is Faster for Strong than for Weak Poly(A) Sites. Mol. Cell. Biol. 19: 5588-5600 [Abstract] [Full Text]  
• Zhao, J., Hyman, L., Moore, C. (1999). Formation of mRNA 3' Ends in Eukaryotes: Mechanism, Regulation, and Interrelationships with Other Steps in mRNA Synthesis. Microbiol. Mol. Biol. Rev. 63: 405-445 [Abstract] [Full Text]  
• Colgan, D. F., Manley, J. L. (1997). Mechanism and regulation of mRNA polyadenylation. Genes Dev. 11: 2755-2766 [Full Text]  
• Graveley, B. R., Fleming, E. S., Gilmartin, G. M. (1996). Restoration of Both Structure and Function to a Defective Poly(A) Site by in Vitro Selection. J. Biol. Chem. 271: 33654-33663 [Abstract] [Full Text]