ArticleAmerican journal of physiology. Renal physiology2011
Role of AUF1 and HuR in the pH-responsive stabilization of phosphoenolpyruvate carboxykinase mRNA in LLC-PK₁-F⁺ cells.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- RNA-binding proteins and their role in kidney disease.Nature reviews. Nephrology · 2022Review
- Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2020Article
- Proximal tubule function and response to acidosis.Clinical journal of the American Society of Nephrology : CJASN · 2014Review
- pH-responsive, gluconeogenic renal epithelial LLC-PK1-FBPase+cells: a versatile in vitro model to study renal proximal tubule metabolism and function.American journal of physiology. Renal physiology · 2014Review
- Expression of glutamine transporter Slc38a3 (SNAT3) during acidosis is mediated by a different mechanism than tissue-specific expression.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2014Article
- Proteomic profiling and pathway analysis of the response of rat renal proximal convoluted tubules to metabolic acidosis.American journal of physiology. Renal physiology · 2013Article
- Renal ammonia metabolism and transport.Comprehensive Physiology · 2013Review
- Concurrent binding and modifications of AUF1 and HuR mediate the pH-responsive stabilization of phosphoenolpyruvate carboxykinase mRNA in kidney cells.American journal of physiology. Renal physiology · 2012Article
- Molecular mechanisms of acid-base sensing by the kidney.Journal of the American Society of Nephrology : JASN · 2012Review
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6 authors at 1 institution in 1 country.
Funding
Abstract
Onset of metabolic acidosis leads to a rapid and pronounced increase in expression of phosphoenolpyruvate carboxykinase (PEPCK) in rat renal proximal convoluted tubules. This adaptive response is modeled by treating a clonal line of porcine LLC-PK(1)-F(+) cells with an acidic medium (pH 6.9, 9 mM HCO(3)(-)). Measurement of the half-lives of PEPCK mRNA in cells treated with normal (pH 7.4, 26 mM HCO(3)(-)) and acidic medium established that the observed increase is due in part to stabilization of the PEPCK mRNA. The pH-responsive stabilization was reproduced in a Tet-responsive chimeric reporter mRNA containing the 3'-UTR of PEPCK mRNA. This response was lost by mutation of a highly conserved AU sequence that binds AUF1 and is the primary element that mediates the rapid turnover of PEPCK mRNA. However, siRNA knockdown of AUF1 had little effect on the basal levels and the pH-responsive increases in PEPCK mRNA and protein. Electrophoretic mobility shift assays established that purified recombinant HuR, another AU element binding protein, also binds with high affinity and specificity to multiple sites within the final 92-nucleotides of the 3'-UTR of the PEPCK mRNA, including the highly conserved AU-rich element. siRNA knockdown of HuR caused pronounced decreases in basal expression and the pH-responsive increases in PEPCK mRNA and protein. Therefore, basal expression and the pH-responsive stabilization of PEPCK mRNA in LLC-PK(1)-F(+) cells, and possibly in the renal proximal tubule, may require the remodeling of HuR and AUF1 binding to the elements that mediate the rapid turnover of PEPCK mRNA.
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