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Papers In Press, published online ahead of print October 18, 2001
J. Biol. Chem, 10.1074/jbc.M104645200
Submitted on May 22, 2001
Revised on October 18, 2001
Accepted on October 18, 2001
Molecular Oncology Group/McGill AIDS Centre, Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2
Corresponding Author: anne.gatignol{at}mcgill.ca
TRBP1 and TRBP2 are isoforms of a double-stranded RNA binding protein that differ by their N-terminal end, and were each identified by binding to HIV-1 TAR RNA. TRBP1 and TRBP2 also bind and modulate the function of the dsRNA activated protein kinase, PKR. Both proteins increase LTR 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 to TRBP1 promoter. In addition, a specific down-regulation of TRBP1 and TRBP2 promoter activity was identified in human astrocytic cell line U251MG compared to HeLa cells. This minimal TRBP promoter activity may account for minimal HIV-1 replication in astrocytes.
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