Nucleic Acids Research Advance Access originally published online on April 10, 2007
Nucleic Acids Research 2007 35(8):2629-2642; doi:10.1093/nar/gkm124
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Nucleic Acids Research, 2007, Vol. 35, No. 8 2629-2642
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
RNA helicase A interacts with divergent lymphotropic retroviruses and promotes translation of human T-cell leukemia virus type 1
1Center for Retrovirus Research, 2Department of Veterinary Biosciences and 3Department of Molecular Virology, Immunology & Medical Genetics, 4Molecular, Cellular & Developmental Biology Graduate Program, 5Center for Biostatistics and 6Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210-1093, USA
*To whom correspondence should be addressed. Tel: +1-614-292-1392; Fax: +1-614-292-6473; Email: boris-lawrie.1{at}osu.edu
Received September 15, 2006. Revised January 25, 2007. Accepted February 14, 2007.
The 5' untranslated region (UTR) of retroviruses contain structured replication motifs that impose barriers to efficient ribosome scanning. Two RNA structural motifs that facilitate efficient translation initiation despite a complex 5' UTR are internal ribosome entry site (IRES) and 5' proximal post-transcriptional control element (PCE). Here, stringent RNA and protein analyses determined the 5' UTR of spleen necrosis virus (SNV), reticuloendotheliosis virus A (REV-A) and human T-cell leukemia virus type 1 (HTLV-1) exhibit PCE activity, but not IRES activity. Assessment of SNV translation initiation in the natural context of the provirus determined that SNV is reliant on a cap-dependent initiation mechanism. Experiments with siRNAs identified that REV-A and HTLV-1 PCE modulate post-transcriptional gene expression through interaction with host RNA helicase A (RHA). Analysis of hybrid SNV/HTLV-1 proviruses determined SNV PCE facilitates Rex/Rex responsive element-independent Gag production and interaction with RHA is necessary. Ribosomal profile analyses determined that RHA is necessary for polysome association of HTLV-1 gag and provide direct evidence that RHA is necessary for efficient HTLV-1 replication. We conclude that PCE/RHA is an important translation regulatory axis of multiple lymphotropic retroviruses. We speculate divergent retroviruses have evolved a convergent RNA–protein interaction to modulate translation of their highly structured mRNA.
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