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Nucleic Acids Research, 1994, Vol. 22, No. 22 4725-4732
© 1994

MOLECULAR BIOLOGY

Rev of human immunodeficiency virus and Rex of the human T-cell leukemia virus type I can counteract and mRNA downregulatory element of the transferrin receptor mRNA

Andrei S. Zolotukhin, Joe B. Harford1,+ and Barbara K. Felber*

Human Retrovirus Pathogenesis Group, National Cencer Institute–Frederick Cancer Research and Development Center, ABL-Basic Research Program Frederick, MD 21702 1Cell Biology and Metabolism Branch NICDH, NIH, Bethesda, MD 20892, USA

*To whom correspondence should be addressed

Received June 30, 1994. Revised October 7, 1994. Accepted October 7, 1994.

Expression of the structural proteins of the human immunodeficiency virus type 1 (HIV-1), the human Tcell leukemia virus type I (HTLV-I), and of the transferrin receptor (TfR) mRNA depends on posttranscriptional regulatory mechanisms involving both positive and negative elements. In these systems the presence of elements decreasing mRNA expression have been demonstrated. The regulatory proteins (Rev, Rex or iron response element binding protein IRE-BP) antagonize the effects of the downregulatory elements by interacting directly with specific mRNA sites (Rev responsive element, RRE, Rex responsive element, RXRE, or iron responsive elements, IREs) resulting in stabilization and efficient expression of the corresponding mRNAs. To investigate whether this strategy involves common pathways of mRNA utilization, we have studied expression from hybrid mRNAs that contained these previously identified HIV-1 or TfR instability determinants and the binding sites of the regulatory proteins Rev, Rex and/or IRE-BP. Our results demonstrate that only low levels of these hybrid mRNAs accumulate in the absence of the positive regulatory factors Rev, Rex or IRE-BP. The presence of these factors counteracts the effect of heterologous downregulatory elements resulting in increased accumulation of the hybrid mRNAs. However, while Rev or Rex regulation also resulted in efficient protein expression, the IRE-BP only affected mRNA levels without significantly affecting protein expression, suggesting that the pathways of mRNA stabilization/expression are different in these systems.

+Present address: RiboGene, 21375 Cabot Blvd, Hayward, CA 94545, USA


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