hnRNP E1 and E2 have distinct roles in modulating HIV-1 gene expression.
Pre-mRNA processing, including 5' end capping, splicing, and 3' end cleavage/polyadenylation, are events coordinated by transcription that can influence the subsequent export and translation of mRNAs. Coordination of RNA processing is crucial in retroviruses such as HIV-1, where inefficient splicing and the export of intron-containing RNAs are required for expression of the full complement of viral proteins. RNA processing can be affected by both viral and cellular proteins, and in this study we demonstrate that a member of the hnRNP E family of proteins can modulate HIV-1 RNA metabolism and expression. We show that hnRNP E1/E2 are able to interact with the ESS3a element of the bipartite ESS in tat/rev exon 3 of HIV-1 and that modulation of hnRNP E1 expression alters HIV-1 structural protein synthesis. Overexpression of hnRNP E1 leads to a reduction in Rev, achieved in part through a decrease in rev mRNA levels. However, the reduction in Rev levels cannot fully account for the effect of hnRNP E1, suggesting that hmRNP E1 might also act to suppress viral RNA translation. Deletion mutagenesis determined that the C-terminal end of hnRNP E1 was required for the reduction in Rev expression and that replacing this portion of hnRNP E1 with that of hnRNP E2, despite the high degree of conservation, could not rescue the loss of function.
Woolaway
Kathryn
K
Department of Molecular and Medical Genetics, University of Toronto Toronto, Ontario, Canada. kew@hotmail.co.uk <kew@hotmail.co.uk>
Asai
Kengo
K
Emili
Andrew
A
Cochrane
Alan
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D015694:Gene Products, rev / Q000096:biosynthesis / Q000235:genetics; D015757:Genes, rev; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054321:rev Gene Products, Human Immunodeficiency Virus
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D015694:Gene Products, rev; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C489559:KHDRBS1 protein, human; C485572:KHDRBS2 protein, human; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1