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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Mapping of the human RNASEL promoter and expression in cancer and normal cells.

2',5'-Oligoadenylate (2-5A)-dependent RNase L is a ubiquitous endoribonuclease of higher vertebrates that functions in the interferon (IFN) antiviral response by degrading both viral and cellular single-stranded RNA (ssRNA). In addition, the RNase L gene, RNASEL, was mapped to the hereditary prostate cancer 1 ( HPC1) gene. Previous analyses of human RNASEL determined its exon/intron structure but lacked a description of the promoter region. We thus mapped the RNASEL transcriptional start site using 5'-rapid amplification of cDNA ends (5'-RACE) and primer extension methods with RNA from human histiocytic lymphoma U937 cells. The promoter sequence was analyzed for potential transcription factor binding sites. Although a canonical IFN-gamma activation site (GAS) element (TTCCAAGAA) was identified (nucleotides -155 to -147), there was only slight induction of RNASEL promoter-reporter activity or of endogenous RNase L expression in response to IFN-alpha or IFN-gamma. Several sites for tissue-specific and general promoters were observed, however, which could explain the widespread expression of RNase L in mammalian cells. Accordingly, RNase L levels were determined and compared in different human and rodent cancer and normal cell types using a radiolabeled 2-5A derivative. In addition, levels of RNase L were established in various normal human tissues and cell types by immunoblotting and immunohistochemistry. Our findings are the first description of the human RNASEL promoter that allows constituitive expression in a range of normal and neoplastic cell types.[1]


  1. Mapping of the human RNASEL promoter and expression in cancer and normal cells. Zhou, A., Molinaro, R.J., Malathi, K., Silverman, R.H. J. Interferon Cytokine Res. (2005) [Pubmed]
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