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PMID:11641396

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Citation

Bannwarth, S, Talakoub, L, Letourneur, F, Duarte, M, Purcell, DF, Hiscott, J and Gatignol, A (2001) Organization of the human tarbp2 gene reveals two promoters that are repressed in an astrocytic cell line. J. Biol. Chem. 276:48803-13

Abstract

TRBP1 and TRBP2 are isoforms of a double-stranded RNA-binding protein that differ in their N-terminal end and were each identified by binding to human immunodeficiency virus type 1 (HIV-1) trans-activation-responsive RNA. TRBP1 and TRBP2 also bind and modulate the function of the double-stranded RNA-activated protein kinase, protein kinase R. Both proteins increase long terminal repeat expression in human and murine cells, and their gene has been mapped to human chromosome 12. We have isolated and characterized the complete tarbp2 gene (5493 bp) coding for the two TRBP proteins. Two adjacent promoters initiate transcription of alternative first exons for TRBP1 and TRBP2 mRNAs that are spliced onto common downstream exons. TRBP2 transcription and translation start sites are localized within the first intron of TRBP1. TRBP promoters are TATA-less but have CCAAT boxes, a CpG island, and several potential binding sites for transcriptional factors. Promoter deletion analysis identified two regions from position -1397 to -330 for TRBP1 and from position -330 to +38 for TRBP2 that are important for promoter function. TRBP2 promoter activity was expressed at a higher level compared with TRBP1 promoter. In addition, a specific down-regulation of TRBP1 and TRBP2 promoter activity was identified in human astrocytic cell line U251MG compared with HeLa cells. This minimal TRBP promoter activity may account for minimal HIV-1 replication in astrocytes.

Links

PubMed Online version:10.1074/jbc.M104645200

Keywords

Alternative Splicing/genetics; Astrocytes/physiology; Base Sequence; Cell Line; Cloning, Molecular; Exons/genetics; Gene Expression Regulation/genetics; HIV-1/genetics; HIV-1/metabolism; HeLa Cells; Humans; Molecular Sequence Data; Nucleic Acid Conformation; Promoter Regions, Genetic/physiology; Protein Isoforms; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA-Binding Proteins/chemistry; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TRBP2

involved_in

GO:0050689: negative regulation of defense response to virus by host

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TRBP2

involved_in

GO:0046782: regulation of viral transcription

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TRBP2

involved_in

GO:0045070: positive regulation of viral genome replication

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TRBP2

involved_in

GO:0006469: negative regulation of protein kinase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

See also

References

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