Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.4 (RNase H)
 2,751 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased expression of rat kidney-type glutaminase (KGA) during metabolic acidosis results from selective mRNA stabilization. This process is mediated by an 8-base AU-sequence that functions as a pH-response element (pHRE). LLC-PK1-FBPase+ cells, a pH-responsive porcine kidney cell line, express four distinct GA mRNAs. RNase H mapping indicated that three of the GA mRNAs are generated by use of alternative polyadenylation sites and are homologs of the rat KGA mRNA, while the fourth contains a different COOH-terminal coding and 3'-untranslated sequence. PCR cloning and sequencing established that the latter GA mRNA is the homolog of the human GAC mRNA. A rat GAC cDNA was also cloned from a rat kidney library. The 3'-untranslated regions of the GAC mRNAs, but not the porcine or human KGA mRNAs, contain identifiable pHREs. The human KGA gene spans 82 kb and is composed of 19 exons. The unique sequence from the hGAC cDNA is contained in a single exon. Thus in humans, alternative splicing of the initial transcript could produce two GA mRNAs, only one of which may be increased during acidosis.
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PMID:Complexity and species variation of the kidney-type glutaminase gene. 1204 96

During chronic metabolic acidosis, increased expression of renal glutaminase (GA) results from selective stabilization of the GA mRNA. This response is mediated by a direct repeat of an 8-base adenylate-uridylate (AU) sequence that binds zeta-crystallin and functions as a pH response element (pH-RE). A tetracycline-responsive promoter system was developed in LLC-PK(1)-F(+) cells to perform pulse-chase analysis of the turnover of a chimeric beta-globin (betaG) mRNA that contains 960 bp of the 3'-UTR of GA mRNA including the pH-RE. The betaG-GA mRNA exhibits a 14-fold increase in half-life when the LLC-PK(1)-F(+) cells are transferred to acidic medium. RNase H cleavage and Northern blot analysis of the 3'-ends established that rapid deadenylation occurred concomitantly with the rapid decay of the betaG-GA mRNA in cells grown in normal medium. Stabilization of the betaG-GA mRNA in acidic medium is associated with a pronounced decrease in the rate of deadenylation. Mutation of the pH-RE within the betaG-GA mRNA blocked the pH-responsive stabilization, but not the rapid decay, whereas insertion of only a 29-bp segment containing the pH-RE was sufficient to produce both a rapid decay and a pH-responsive stabilization. Various kidney cells express multiple isoforms of AUF1, an AU-binding protein that enhances mRNA turnover. RNA gel-shift assays demonstrated that the recombinant p40 isoform of AUF1 binds to the pH-RE with high affinity and specificity. Thus AUF1 may mediate the rapid turnover of the GA mRNA, whereas increased binding of zeta-crystallin during acidosis may inhibit degradation and result in selective stabilization.
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PMID:Role of deadenylation and AUF1 binding in the pH-responsive stabilization of glutaminase mRNA. 1621 14