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10.1172/jci.insight.94375 http://scihub22266oqcxt.onion/10.1172/jci.insight.94375 C5846909!5846909!29046474     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29046474&cmd=llinks): Failed to open stream: HTTP request failed! 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Human alternative Klotho mRNA is a nonsense-mediated mRNA decay target inefficiently spliced in renal disease |pdf=|usr=}}{{29046474}} gab.com Text Human alternative Klotho mRNA is a nonsense-mediated mRNA decay target inefficiently spliced in renal disease JO: JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=29046474 #FOAvip Klotho is a renal protein involved in phosphate homeostasis, which is downregulated in renal disease. It has long been considered an antiaging factor. Two Klotho gene transcripts are thought to encode membrane-bound and secreted Klotho. Indeed, soluble Klotho is detectable in bodily fluids, but the relative contributions of Klotho secretion and of membrane-bound Klotho shedding are unknown. Recent advances in RNA surveillance reveal that premature termination codons, as present in alternative Klotho mRNA (for secreted Klotho), prime mRNAs for degradation by nonsense-mediated mRNA decay (NMD). Disruption of NMD led to accumulation of alternative Klotho mRNA, indicative of normally continuous degradation. RNA IP for NMD core factor UPF1 resulted in enrichment for alternative Klotho mRNA, which was also not associated with polysomes, indicating no active protein translation. Alternative Klotho mRNA transcripts colocalized with some P bodies, where NMD transcripts are degraded. Moreover, we could not detect secreted Klotho in vitro. These results suggest that soluble Klotho is likely cleaved membrane-bound Klotho only. Furthermore, we found that, especially in acute kidney injury, splicing of the 2 mRNA transcripts is dysregulated, which was recapitulated by various noxious stimuli in vitro. This likely constitutes a novel mechanism resulting in the downregulation of membrane-bound Klotho. Twit Text FOAVip Human alternative Klotho mRNA is a nonsense-mediated mRNA decay target inefficiently spliced in renal disease ????JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=29046474 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29046474 #FOAvip English Wikipedia <ref>{{Cite pmid|29046474}}</ref> Human alternative Klotho mRNA is a nonsense-mediated mRNA decay target inefficiently spliced in renal disease #MMPMID29046474 Mencke R; Harms G; Moser J; van Meurs M; Diepstra A; Leuvenink HG; Hillebrands JL JCI Insight ä[]; 2 (20): ä PMID29046474show ga Klotho is a renal protein involved in phosphate homeostasis, which is downregulated in renal disease. It has long been considered an antiaging factor. Two Klotho gene transcripts are thought to encode membrane-bound and secreted Klotho. Indeed, soluble Klotho is detectable in bodily fluids, but the relative contributions of Klotho secretion and of membrane-bound Klotho shedding are unknown. Recent advances in RNA surveillance reveal that premature termination codons, as present in alternative Klotho mRNA (for secreted Klotho), prime mRNAs for degradation by nonsense-mediated mRNA decay (NMD). Disruption of NMD led to accumulation of alternative Klotho mRNA, indicative of normally continuous degradation. RNA IP for NMD core factor UPF1 resulted in enrichment for alternative Klotho mRNA, which was also not associated with polysomes, indicating no active protein translation. Alternative Klotho mRNA transcripts colocalized with some P bodies, where NMD transcripts are degraded. Moreover, we could not detect secreted Klotho in vitro. These results suggest that soluble Klotho is likely cleaved membrane-bound Klotho only. Furthermore, we found that, especially in acute kidney injury, splicing of the 2 mRNA transcripts is dysregulated, which was recapitulated by various noxious stimuli in vitro. This likely constitutes a novel mechanism resulting in the downregulation of membrane-bound Klotho. äHuman alternative Klotho mRNA is a nonsense-mediated mRNA decay target(epmc).pdf DeepDyve Pubget Overpricing