Murine Pth mRNA is bound by ARE-BPs, which either stabilize or
destabilize Pth mRNA, thereby altering Pth mRNA
half-life. The ratio of activities of stabilizing/destabilizing ARE-BPs bound to
Pth mRNA determines the half-life of a given
Pth mRNA molecule. KSRP is a Pth
mRNA–destabilizing ARE-BP that is active in its dephosphorylated
state. In their new study in this issue of the JCI, Nechama et
al. (46) report that the peptidyl-prolyl
isomerase Pin1 is responsible for the dephosphorylation of KSRP. In CKD, Pin1
activity is reduced, and as a result, less dephosphorylated (active) KSRP is
available. As a consequence, a stabilizing ARE-BP, AUF1, is active and
Pth mRNA is degraded to a lesser extent, resulting in higher
intracellular Pth mRNA levels, more PTH synthesis, and secondary
hyperparathyroidism. P, phosphate.