Regulation of Parathyroid Hormone mRNA Stability by Calcium and Phosphate

2007 ◽  
pp. 57-67 ◽  
Author(s):  
Rachel Kilav ◽  
Justin Silver ◽  
Tally Naveh-Many
Keyword(s):  
Parathyroid Hormone ◽  
Mrna Stability

scholarly journals Cisandtransacting factors in the regulation of parathyroid hormone (PTH) mRNA stability by calcium and phosphate

FEBS Letters ◽  
2002 ◽  
Vol 529 (1) ◽  
pp. 60-64 ◽  
Author(s):  
Tally Naveh-Many ◽  
Osnat Bell ◽  
Justin Silver ◽  
Rachel Kilav
Keyword(s):  
Parathyroid Hormone ◽  
Mrna Stability

scholarly journals Epidermal growth factor-stimulated parathyroid hormone-related protein expression involves increased gene transcription and mRNA stability

1995 ◽  
Vol 307 (1) ◽  
pp. 159-167 ◽  
Author(s):  
J K Heath ◽  
J Southby ◽  
S Fukumoto ◽  
L M O'Keeffe ◽  
T J Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parathyroid Hormone ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Gene Transcription ◽  
Mrna Stability ◽  
Specific Effect ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Epidermal Growth

Epidermal growth factor (EGF) produced rapid and striking effects on parathyroid hormone-related protein (PTHrP) gene expression in the immortalized human keratinocyte cell line, HaCaT. Steady-state levels of PTHrP mRNA and secreted PTHrP were increased 10-fold by maximally effective concentrations of EGF. EGF increased both PTHrP gene transcription and PTHrP mRNA stability. Nuclear run-on assays demonstrated a 4-fold increase in transcriptional rate in EGF-stimulated cells while transient transfection analysis indicated that the action of EGF on transcription involved both the GC-rich promoter, P2, and the downstream TATA promoter, P3, but apparently not the upstream TATA promoter, P1. In experiments where EGF treatment produced more stable PTHrP transcripts, the half-life of c-fos mRNA was unaltered, suggesting a relatively specific effect of EGF. Moreover, only those species of PTHrP mRNA containing two of the alternative 3′ exons (exons VII and VIII) were stable, those containing exon IX were not. Reverse-transcription PCR demonstrated that EGF produced differential increases in the abundance of PTHrP mRNA species initiated by the three PTHrP promoters. The major effect was seen on the abundance of transcripts initiated by P1 and P2, with less marked regulation of P3-initiated transcripts. Thus EGF regulation of PTHrP gene expression in HaCaT cells is multifactorial and the combination of its actions at the 5′ and 3′ ends of the gene favours the accumulation of subpopulations of PTHrP mRNA containing exons I, VII and VIII.

scholarly journals Parathyroid Hormone (PTH) decreases mRNA stability of the Type IIa Sodium‐Phosphate Cotransporter (NpT2a)

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Rebecca Murray ◽  
Nina Lesousky ◽  
Syed Jalal Khundmiri ◽  
Barbara Clark ◽  
Eleanor Lederer
Keyword(s):  
Parathyroid Hormone ◽  
Mrna Stability ◽  
Sodium Phosphate

scholarly journals Chronic kidney disease alters Pin1 phosphorylation and parathyroid hormone mRNA binding proteins leading to secondary hyperparathyroidism

2021 ◽  
Author(s):  
Alia Hasan ◽  
Yael E. Pollak ◽  
Rachel Levin ◽  
Justin Silver ◽  
Nir London ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Mrna Stability ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Chronic Kidney Failure ◽  
Mrna Binding Proteins ◽  
Mrna Binding

AbstractParathyroid hormone (PTH) regulates calcium metabolism and bone strength. Chronic kidney disease (CKD) leads to secondary hyperparathyroidism (SHP) which increases morbidity and mortality. High PTH expression in SHP is due to increased PTH mRNA stability mediated by changes in PTH mRNA interaction with stabilizing AUF1 and destabilizing KSRP. Pin1 isomerizes target proteins, including mRNA binding proteins. In SHP, Pin1 isomerase activity is decreased and phosphorylated KSRP fails to bind PTH mRNA, resulting in high PTH mRNA stability and levels. The molecular mechanisms underlying Pin1 regulation and their effect to increase PTH expression are unknown. We show by mass-spectrometry (MS) the CKD induced changes in rat parathyroid proteome and phosphoproteome profiles. Parathyroid Pin1 Ser16 and Ser71 phosphorylation, that disrupts Pin1 activity, is enhanced in acute and chronic kidney failure rats. Accordingly, pharmacologic Pin1 inhibition increases PTH expression in parathyroid organ cultures and transfected cells, through the PTH mRNA protein binding cis element and KSRP phosphorylation. Therefore, CKD leads to parathyroid loss of Pin1 activity by inducing Pin1 phosphorylation. This predisposes parathyroids to increase PTH production through modified PTH mRNA-KSRP interaction that is dependent on KSRP phosphorylation. CKD induced Pin1 and KSRP phosphorylation and the Pin1-KSRP-PTH mRNA axis thus drive secondary hyperparathyroidism.

scholarly journals Pin1 regulates parathyroid hormone mRNA stability

2009 ◽  
Vol 119 (10) ◽  
pp. 2887-2891 ◽  
Author(s):  
Rajiv Kumar
Keyword(s):  
Parathyroid Hormone ◽  
Mrna Stability

scholarly journals Mechanism of Increased Parathyroid Hormone mRNA in Experimental Uremia

1999 ◽  
Vol 10 (12) ◽  
pp. 2562-2568
Author(s):  
CEVDET YALCINDAG ◽  
JUSTIN SILVER ◽  
TALLY NAVEH-MANY
Keyword(s):  
Renal Failure ◽  
Parathyroid Hormone ◽  
Chronic Renal Failure ◽  
Protein Binding ◽  
Secondary Hyperparathyroidism ◽  
Mrna Stability ◽  
Rna Degradation ◽  
Cross Linking ◽  
Mrna Levels

Abstract. Patients with chronic renal failure develop secondary hyperparathyroidism with increased synthesis and secretion of parathyroid hormone (PTH) resulting in severe skeletal complications. In rats with secondary hyperparathyroidism due to 5/6 nephrectomy, there are increased PTH mRNA levels, and this mechanism was studied. Parathyroid glands were micro-dissected from control and 5/6 nephrectomy rats and analyzed for PTH mRNA and control genes, and the nuclei were used for nuclear run-on experiments. The cytosolic proteins of the parathyroids were used to study PTH mRNA protein binding by ultraviolet cross-linking and the degradation of the PTH transcript in vitro. Nuclear run-ons showed that the increase in PTH mRNA levels was posttranscriptional. Protein binding to the PTH mRNA 3′-UTR determines PTH mRNA stability and levels. Parathyroid proteins from uremic rats bound PTH mRNA similar to control rats by ultraviolet cross-linking. To determine the effect of uremia on PTH mRNA stability, an in vitro RNA degradation assay was performed with parathyroid proteins from uremic rats. When parathyroid proteins from control rats were incubated with PTH mRNA, there was transcript degradation already at 30 min, reaching 50% at 60 min and 90% at 180 min. With uremic parathyroid proteins, the PTH mRNA was not degraded at all at 120 min and was moderately decreased at 180 min. This decrease in degradation by uremic parathyroid proteins suggests a decrease in parathyroid cytosolic endonuclease activity in uremia resulting in a more stable PTH transcript. The increased PTH mRNA levels would translate into increased PTH synthesis and serum PTH levels, which would lead to metabolic bone disease in many patients with chronic renal failure.

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