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

Naveh-Many, Tally; Bell, Osnat; Silver, Justin; Kilav, Rachel

doi:10.1016/s0014-5793(02)03259-3

Cited by 36 publications

(24 citation statements)

References 25 publications

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“…The alternate explanation, that Ca regulates PTH mRNA stability, was supported by their in vitro degradation assays. Subsequent studies identified a cis element in the 3 0 -UTR of rat PTH that targeted reporter transcripts for degradation and that bound cytosolic proteins in a Ca-dependent manner (Moallem et al 1998, Sela-Brown et al 1999, 2000, Kilav et al 2001, Naveh-Many et al 2002; human and bovine 3 0 -UTR were found to have alternative cis-acting protein-binding elements involved in the stabilization of PTH mRNA (Bell Destabilization of PTH mRNA . C S RITTER and others 17 et al 2005a).…”

Section: Discussionmentioning

confidence: 99%

Destabilization of parathyroid hormone mRNA by extracellular Ca2+ and the calcimimetic R-568 in parathyroid cells: role of cytosolic Ca and requirement for gene transcription

Ritter

Pande²,

Krits³

et al. 2007

Journal of Molecular Endocrinology

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Extracellular Ca reduces parathyroid hormone (PTH) levels through several mechanisms, but many details of the intracellular steps involved have been difficult to elucidate because of the lack of a suitable parathyroid cell model. The present studies utilized our Ca-responsive bovine parathyroid organoid culture system (pseudoglands) to examine PTH mRNA in intact parathyroid cells. Increasing medium calcium from 0 . 4 to 3 . 0 mM reduced PTH mRNA to 20-30% of basal by 16 h. Reducing medium Ca from 3 . 0 to 0 . 4 mM restored PTH mRNA levels over a 24-h period. PTH mRNA was also reduced by the calcimimetic R-568, confirming the role of the calcium-sensing receptor. PTH decay rates were determined by placing pseudoglands in either 0 . 4 or 3 . 0 mM Ca for 2 h and then blocking gene transcription. PTH mRNA remained stable for at least 24 h in pseudoglands incubated in 0 . 4 mM Ca, but fell gradually by 62% in the presence of 3 . 0 mM Ca. Blocking transcription prior to the addition of high-Ca medium dramatically blunted the Ca-induced degradation of PTH mRNA, indicating that acceleration of PTH mRNA decay by Ca requires gene transcription. Pharmacologic investigation of the signaling pathways involved indicated that the Ca-induced reduction of PTH mRNA did not involve MAP kinase, phospholipase D, or cyclic AMP. However, increasing cytosolic Ca with thapsigargin or the Ca ionophore A23187 decreased PTH mRNA levels. In summary, Ca-mediated destabilization of PTH mRNA requires gene transcription and involves increases in cytosolic Ca.

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Section: Discussionmentioning

confidence: 99%

Destabilization of parathyroid hormone mRNA by extracellular Ca2+ and the calcimimetic R-568 in parathyroid cells: role of cytosolic Ca and requirement for gene transcription

Ritter

Pande²,

Krits³

et al. 2007

Journal of Molecular Endocrinology

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“…The 63-nt element consists of a core 26-nt minimal binding sequence and adjacent flanking regions. The Pth RNA ARE does not contain AUUUA sequences and falls into the class III category of AREs (42,43). Two proteins, AU-rich binding factor 1 (AUF1) and K-homology splicing regulator protein (KSRP), bind the ARE in the 3′ UTR of Pth mRNA (43,44).…”

Section: Figurementioning

confidence: 99%

“…The Pth RNA ARE does not contain AUUUA sequences and falls into the class III category of AREs (42,43). Two proteins, AU-rich binding factor 1 (AUF1) and K-homology splicing regulator protein (KSRP), bind the ARE in the 3′ UTR of Pth mRNA (43,44). AUF1 increases Pth mRNA half-life, whereas KSRP has the opposite effect (43,44).…”

Section: Figurementioning

confidence: 99%

“…Two proteins, AU-rich binding factor 1 (AUF1) and K-homology splicing regulator protein (KSRP), bind the ARE in the 3′ UTR of Pth mRNA (43,44). AUF1 increases Pth mRNA half-life, whereas KSRP has the opposite effect (43,44). Both proteins are regulated by changes in serum Ca 2+ and Pi concentrations and are altered by CKD (43,45).…”

Section: Figurementioning

confidence: 99%

“…AUF1 increases Pth mRNA half-life, whereas KSRP has the opposite effect (43,44). Both proteins are regulated by changes in serum Ca 2+ and Pi concentrations and are altered by CKD (43,45). (Figure 2).…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Pin1 regulates parathyroid hormone mRNA stability

Kumar

2009

J. Clin. Invest.

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The RNA‐binding protein HuD: a regulator of neuronal differentiation, maintenance and plasticity

2006

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mRNA stability is increasingly recognized as being essential for controlling the expression of a wide variety of transcripts during neuronal development and synaptic plasticity. In this context, the role of AU-rich elements (ARE) contained within the 3' untranslated region (UTR) of transcripts has now emerged as key because of their high incidence in a large number of cellular mRNAs. This important regulatory element is known to significantly modulate the longevity of mRNAs by interacting with available stabilizing or destabilizing RNA-binding proteins (RBP). Thus, in parallel with the emergence of ARE, RBP are also gaining recognition for their pivotal role in regulating expression of a variety of mRNAs. In the nervous system, the member of the Hu family of ARE-binding proteins known as HuD, has recently been implicated in multiple aspects of neuronal function including the commitment and differentiation of neuronal precursors as well as synaptic remodeling in mature neurons. Through its ability to interact with ARE and stabilize multiple transcripts, HuD has now emerged as an important regulator of mRNA expression in neurons. The present review is designed to provide a comprehensive and updated view of HuD as an RBP in the nervous system. Additionally, we highlight the role of HuD in multiple aspects of a neuron's life from early differentiation to changes in mature neurons during learning paradigms and in response to injury and regeneration. Finally, we describe the current state of knowledge concerning the molecular and cellular events regulating the expression and activity of HuD in neurons.

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

Cited by 36 publications

References 25 publications

Destabilization of parathyroid hormone mRNA by extracellular Ca2+ and the calcimimetic R-568 in parathyroid cells: role of cytosolic Ca and requirement for gene transcription

Destabilization of parathyroid hormone mRNA by extracellular Ca2+ and the calcimimetic R-568 in parathyroid cells: role of cytosolic Ca and requirement for gene transcription

Pin1 regulates parathyroid hormone mRNA stability

The RNA‐binding protein HuD: a regulator of neuronal differentiation, maintenance and plasticity

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