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Am J Physiol Renal Physiol 284: F663-F670, 2003. First published December 10, 2002; doi:10.1152/ajprenal.00332.2002
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Vol. 284, Issue 4, F663-F670, April 2003

Characterization of cis-acting element in renal NaPi-2 cotransporter mRNA that determines mRNA stability

Yulia Moz, Justin Silver, and Tally Naveh-Many

Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah University Hospital, Jerusalem, Israel 91120

Hypophosphatemia leads to an increase in Na+-Pi cotransporter (NaPi-2) mRNA levels. This increase is posttranscriptional and correlates with a more stable transcript mediated by the terminal 698 nt of the NaPi-2 mRNA. A 71-nt binding element was identified with renal proteins from rats fed control and low-Pi (-Pi) diet. The binding of -Pi renal proteins to this transcript was increased compared with control proteins. The functionality of the cis element was demonstrated by an in vitro degradation assay. -Pi renal proteins stabilized transcripts that included the cis element compared with control renal extracts. The full-length NaPi-2 transcript, but not control transcripts, was stabilized by -Pi extracts. Insertion of the binding element into green fluorescent protein (GFP) as a reporter gene decreased chimeric GFP mRNA levels in transfection experiments. Our results suggest that the protein-binding region of the NaPi-2 mRNA functions as a cis-acting instability element. In hypophosphatemia there is increased binding to the cis-acting element and subsequent stabilization of NaPi-2 mRNA.

phosphate; messenger ribonucleic acid half-life; protein-ribonucleic acid interactions


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