A novel function for Sam68: enhancement of HIV-1 RNA 3' end processing.
Both cis elements and host cell proteins can significantly affect HIV-1 RNA processing and viral gene expression. Previously, we determined that the exon splicing silencer (ESS3) within the terminal exon of HIV-1 not only reduces use of the adjacent 3' splice site but also prevents Rev-induced export of the unspliced viral RNA to the cytoplasm. In this report, we demonstrate that loss of unspliced viral RNA export is correlated with the inhibition of 3' end processing by the ESS3. Furthermore, we find that the host factor Sam68, a stimulator of HIV-1 protein expression, is able to reverse the block to viral RNA export mediated by the ESS3. The reversal is associated with a stimulation of 3' end processing of the unspliced viral RNA. Our findings identify a novel activity for the ESS3 and Sam68 in regulating HIV-1 RNA polyadenylation. Furthermore, the observations provide an explanation for how Sam68, an exclusively nuclear protein, modulates cytoplasmic utilization of the affected RNAs. Our finding that Sam68 is also able to enhance 3' end processing of a heterologous RNA raises the possibility that it may play a similar role in regulating host gene expression.
McLaren
Meredith
M
Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Asai
Kengo
K
Cochrane
Alan
A
D020413:3' Untranslated Regions / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D004268:DNA-Binding Proteins; D005091:Exons / Q000235:genetics; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D019061:src-Family Kinases