Cis and trans acting factors in the regulation of parathyroid hormone (PTH) mRNA stability by calcium and phosphate

FEBS Letters

Kilav, Rachel¹  Bell, Osnat¹  Naveh-Many, Tally¹  Silver, Justin¹ 

[1] Minerva Center for Calcium and Bone Metabolism, Hadassah University Hospital, P.O. Box 12000, Jerusalem 91120, Israel

关键词: Parathyroid hormone gene;    Calcium;    Phosphate;    RNA stability;    3′-Untranslated region;    Protein–RNA binding;    A+U-rich element binding factor 1;    PTH;    parathyroid hormone;    PT;    parathyroid;    AUF1;    A+U-rich element binding factor;    LC8;    dynein light chain (M r 8000);    REMSA;    RNA electrophoretic mobility shift assay;    Ca2+;    calcium;    Pi;    phosphate;   

DOI  :  10.1016/S0014-5793(02)03259-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Calcium and phosphate regulate parathyroid hormone (PTH) mRNA stability through differences in binding of parathyroid proteins to an element in its 3′-untranslated region. One of the proteins is AUF1 (A+U-rich element binding factor 1). An in vitro degradation assay showed that transcripts for PTH and chimeric growth hormone (GH)–PTH 63 nt, but not for native GH, were stabilized by PT proteins from rats on low calcium diets and destabilized by proteins from rats on low phosphate diets, correlating with PTH mRNA levels in vivo. In transfection experiments the 63 nt binding element destabilized mRNAs of reporter genes and this was prevented by over-expression of AUF1. Our results identified a functional cis element in PTH mRNA. Differences in protein binding to this element determine PTH mRNA stability and its regulation by calcium and phosphate.

【 授权许可】

Unknown