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Mol Cell Biol. 1993 October; 13(10): 6180-6189

Rev and the fate of pre-mRNA in the nucleus: implications for the regulation of RNA processing in eukaryotes.

M H Malim and B R Cullen

Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6148.

ABSTRACT

Although a great deal is known about the regulation of gene expression in terms of transcription, relatively little is known about the modulation of pre-mRNA processing. In this study, we exploited a genetically regulated system, human immunodeficiency virus type 1 (HIV-1) and its trans-activator Rev, to examine events that occur between the synthesis of pre-mRNA in the nucleus and the translation of mRNA in the cytoplasm. Unlike the majority of eukaryotic pre-mRNAs whose introns are efficiently recognized and spliced prior to nucleocytoplasmic transport, HIV-1 mRNAs containing functional introns must be exported to the cytoplasm for the expression of many viral proteins. Using human T cells containing stably integrated proviruses, we demonstrate that such incompletely spliced viral mRNAs are exported to the cytoplasm only in the presence of the Rev trans-activator. In the absence of Rev, these intron-containing RNAs are sequestered in the T-cell nucleus and either spliced or, more commonly, degraded. Because Rev does not inhibit the expression of fully spliced viral mRNA species in T cells, we propose that Rev, rather than inhibiting viral pre-mRNA splicing, is acting here both to prevent the nuclear degradation of HIV-1 pre-mRNAs and to induce their translocation to the cytoplasm. Taken together, these findings indicate that the cellular factors responsible for the nuclear retention of unspliced pre-mRNAs, although most probably splicing factors, do not invariably commit these RNAs to productive splicing and can, instead, program such transcripts for degradation.

Mol Cell Biol. 1993 October; 13(10): 6180-6189




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  • Dundr, M, Leno, G., Hammarskjold, M., Rekosh, D, Helga-Maria, C, Olson, M. (1995). The roles of nucleolar structure and function in the subcellular location of the HIV-1 Rev protein. J. Cell Sci. 108: 2811-2823 [Abstract]  
  • Meyer, B E, Malim, M H (1994). The HIV-1 Rev trans-activator shuttles between the nucleus and the cytoplasm.. Genes Dev. 8: 1538-1547 [Abstract]  


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