The RNA binding protein nuclear factor 90 functions as both a positive and negative regulator of gene expression in mammalian cells.
Nuclear factor 90 (NF90) was originally isolated in a complex that binds to the antigen recognition response element (ARRE-2) present in the interleukin-2 promoter. To characterize the transcriptional properties of NF90 in mammalian cells, we examined its ability to modulate promoter function in cellular transfection assays. NF90-Gal4 fusion proteins inhibited transcription from the adenovirus major late promoter in a fashion that was dependent on Gal4 targeting. Conversely, NF90 activated the cytomegalovirus immediate-early promoter, to which it was not targeted. These effects required distinct but overlapping domains in the C terminus of NF90, which contains a functional nuclear localization signal and two double-stranded-RNA binding motifs. NF90 is present in cellular complexes together with the NF45 protein. Transfection assays showed that NF45 binds NF90 strongly and stimulates its ability to activate but not to inhibit gene expression. This report characterizes NF90 as both a positive and negative regulator of gene expression, depending on the promoter context, and suggests a role for NF45 as a regulator of NF90.
Reichman
Trevor W
TW
Department of Biochemistry and Molecular Biology, New Jersey Medical School and Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07013-2714, USA.
Muñiz
Luis C
LC
Mathews
Michael B
MB
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D051903:Nuclear Factor 45 Protein; D050779:Nuclear Factor 90 Proteins; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics* / Q000502:physiology; D014162:Transfection
D004268:DNA-Binding Proteins; C494013:ILF2 protein, human; D050778:NFATC Transcription Factors; D051903:Nuclear Factor 45 Protein; D050779:Nuclear Factor 90 Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D008156:Luciferases