Nucleic Acids Research Advance Access published online on July 4, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn411
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p100 increases AT1R expression through interaction with AT1R 3'-UTR
1Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, 2Protein Chemistry Research Group, Institute of Biotechnology, University of Helsinki, 3Institute of Medical Technology, University of Tampere, 4Department of Clinical Microbiology, Tampere University Hospital, 5Department of Medicine and 6Department of Cardiology, University of Helsinki, Finland
*To whom correspondence should be addressed. Tel: +358 9 47171933; Fax: +358 9 47171921; Email: kpaukku{at}mappi.helsinki.fi
Received May 9, 2008. Revised June 10, 2008. Accepted June 10, 2008.
p100 protein (SND1, Tudor-SN) is a multifunctional protein that functions as a co-activator for several transcription factors, has a role in mRNA processing and participates in RNAi-induced silencing complex (RISC) with yet unknown function. In this study we identified a novel function for p100 as a regulator of angiotensin II type 1 receptor (AT1R) expression. The binding of p100 to AT1R 3'-untranslated region (3'-UTR) via staphylococcal nuclease-like (SN-like) domains increased receptor expression by decreasing the rate of mRNA decay and enhancing its translation. Overexpression of p100 increased AT1R expression, whereas decrease in p100 binding to 3'-UTR either by p100 silencing or by the deletion of p100 binding site downregulated receptor expression. The effect of p100 through AT1R 3'-UTR was independent of Argonaute2 (Ago2), a known p100 partner, and was thus RISC-independent. Nucleotides 118 to 120 of the AT1R 3'-UTR were found to be critical for the binding of p100 to 3'-UTR. In summary, p100 is a multifunctional regulator of gene expression that regulates transcription, mRNA maturation, and as described in this article, also mRNA stability and translation.
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