The Role of AUF1 in AU-rich interleukin-6 mRNA regulation - Dogar, Afzal M.
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The AU-rich elements (AREs) consisting of repeated AUUUA motifs confer rapid degradation to many cellular mRNAs when present in the 3' untranslated region (3'UTR). We have studied the instability of interleukin-6 mRNA by grafting its 3'UTR to a stable green fluorescent protein mRNA. Subsequent scanning mutagenesis identified two conserved elements, which taken together account for most of the instability. Destabilization of ARE-containing mRNAs is thought to involve ARE-binding proteins such as AUF1. We tested whether AUF1 binding to interleukin-6 mRNA correlates with decreased mRNA stability.…mehr

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Produktbeschreibung
The AU-rich elements (AREs) consisting of repeated AUUUA motifs confer rapid degradation to many cellular mRNAs when present in the 3' untranslated region (3'UTR). We have studied the instability of interleukin-6 mRNA by grafting its 3'UTR to a stable green fluorescent protein mRNA. Subsequent scanning mutagenesis identified two conserved elements, which taken together account for most of the instability. Destabilization of ARE-containing mRNAs is thought to involve ARE-binding proteins such as AUF1. We tested whether AUF1 binding to interleukin-6 mRNA correlates with decreased mRNA stability. Overexpression of myc-tagged p37AUF1 and p42AUF1 as well as suppression of all four AUF1 isoforms by RNA interference stabilized the interleukin-6 mRNA. Furthermore, the interleukin-6 mRNA co-immunoprecipitated specifically with myc-tagged p37AUF1 and p42AUF1 in cell extracts. These results indicate that AUF1 binds to the AU-rich element in vivo and promotes interleukin-6 mRNA degradation. The combination of mRNA co-immunoprecipitation with microarray technology revealed that at least 500 cellular mRNAs associate with AUF1.
Autorenporträt
Afzal M. Dogar was born in 1976 in Sahiwal, Pakistan. At the University of Agriculture, Faisalabad has obtained BSc (Hons) degree. He obtained MPhil Biotechnology degree from NIBGE Faisalabad and Quaid-i-Azam University Islamabad. He attended FMI Basel for training and finally pursued the title of PhD at ISREC and University of Lausanne.