The unfolded protein response affects readthrough of premature termination codons. Issue 5 (4th April 2014)

• Record Type: Journal Article
• Authors: Oren, Yifat S; McClure, Michelle L; Rowe, Steven M; Sorscher, Eric J; Bester, Assaf C; Manor, Miriam; Kerem, Eitan; Rivlin, Joseph; Zahdeh, Fouad; Mann, Matthias; Geiger, Tamar; Kerem, Batsheva
• Is Part Of: EMBO molecular medicine. Volume 6:Issue 5(2014:May)
• Page Start: 685
• Page End: 701
• Publication Date: 2014-04-04
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.1002/emmm.201303347
• Languages: English
• ISSNs: 1757-4676

Abstract

<abstract abstract-type="synopsis" xml:lang="en" id="emmm201303347-abs-0002"> <title>Synopsis</title> <p> <boxed-text content-type="graphic" id="emmm201303347-blkfxd-0001" position="anchor" orientation="portrait"> <graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg5nprc1bd" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /> </boxed-text> </p> <p>Activation of the unfolded protein response (UPR) governs the response to readthrough treatment by regulating the levels of transcripts with PTCs. Furthermore, a novel nonsense‐mediated mRNA decay (NMD)‐UPR feedback loop is described.</p> <p> <list id="emmm201303347-list-0001" list-type="bullet"> <list-item> <p>Proteome analyses show substantial differences in unfolded protein response (UPR) activation between patients carrying PTCs, correlated with their response to readthrough treatment.</p> </list-item> <list-item> <p>UPR activation enables CFTR and XLF function following readthrough treatment.</p> </list-item> <list-item> <p>Proteome analyses uncover inverse correlation between UPR and nonsense‐mediated mRNA decay (NMD), suggesting a feedback‐loop mechanism between these homeostatic pathways.</p> </list-item> <list-item> <p>The NMD‐UPR feedback loop augments both UPR activation and NMD attenuation.</p> </list-item> <list-item> <p>The NMD‐UPR feedback loop enhances the response to readthrough treatment, highlighting its clinical importance.</p> </list-item> </list> </p> </abstract>