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

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.