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Impairment of ribosome function activates the MAPKKK ZAK, leading to activation of mitogen-activated protein (MAP) kinases p38 and JNK and inflammatory signaling. The mechanistic basis for activation of this ribotoxic stress response (RSR) remains completely obscure. We show that the long isoform of ZAK (ZAKα) directly associates with ribosomes by inserting its flexible C terminus into the ribosomal intersubunit space. Here, ZAKα binds helix 14 of 18S ribosomal RNA (rRNA). An adjacent domain in ZAKα also probes the ribosome, and together, these sensor domains are critically required for RSR activation after inhibition of both the E-site, the peptidyl transferase center (PTC), and ribotoxin action. Finally, we show that ablation of the RSR response leads to organismal phenotypes and decreased lifespan in the nematode Caenorhabditis elegans (C. elegans). Our findings yield mechanistic insight into how cells detect ribotoxic stress and provide experimental in vivo evidence for its physiological importance.
Pubmed ID: 32289254
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Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.
View all literature mentionsA free reference manager and academic social network to organize your research, collaborate with others online, and discover the latest research. Automatically generate bibliographies, Collaborate easily with other researchers online, Easily import papers from other research software, Find relevant papers based on what you're reading, Access your papers from anywhere online, Read papers on the go with the iPhone app. The software, Mendeley Desktop, offers: * Automatic extraction of document details * Efficient management of your papers * Sharing and synchronization of your library (or parts of it) * Additional features: A plug-in for citing your articles in Microsoft Word, OCR (image-to-text conversion, so you can full-text search all your scanned PDFs), etc The website, Mendeley Web, complements Mendeley Desktop by offering these features: * An online back up of your library * Statistics of all things interesting * A research network that allows you to keep track of your colleagues' publications, conference participations, awards etc * A recommendation engine for papers that might interest you
View all literature mentionsUltrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.
View all literature mentionsWeb server to predict natively disordered regions of protein chain from its amino acid sequence. Returns disorder probability of each residue as prediction results.
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