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Am J Physiol Renal Physiol (December 10, 2002). doi:10.1152/ajprenal.00332.2002
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Articles in PresS, published online ahead of print December 10, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00332.2002
Submitted on September 16, 2002
Accepted on December 3, 2002

Characterization of a cis-acting elment in the renal NaPi-2 co-transporter mRNA that determines mRNA stability

Yulia Moz1, Justin Silver1, and Tally Naveh-Many1*

1 Minerva Center for Calcium and Bone Metabolism, Nephrology and Hypertension, Hadassah University Hospital, Jerusalem, Israel

* To whom correspondence should be addressed. E-mail: tally{at}huji.ac.il.

Hypophosphatemia leads to an increase in Na+-Pi co-transporter (NaPi-2) mRNA levels. This increase is post-transcriptional and correlates with a more stable transcript mediated by the terminal 698 nt of the NaPi-2mRNA. A 71 nt binding element was identified using renal proteins from rats fed control and low Pi diet. The binding of (-) Pi renal proteins to this transcript was increased compared to 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 to control renal extracts. The full-length NaPi-2 transcript, but not control transcripts, was stabilized by (-) Pi extracts. Insertion of the binding element into 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.




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