title: Quantitative proteome analysis reveals RNA processing factors as modulators of ionizing radiation-induced apoptosis in the C. elegans germline.
abstract: The nematode  Caenorhabditis elegans  is an organism most recognized for forward and reverse genetic and functional genomic approaches. Proteomic analyses of DNA damage-induced apoptosis have not been shown because of a limited number of cells undergoing apoptosis. We applied mass spectrometry-based quantitative proteomics to evaluate protein changes induced by ionizing radiation (IR) in isolated C. elegans germlines. For this purpose, we used isobaric peptide termini labeling (IPTL) combined with the data analysis tool IsobariQ, which utilizes MS/MS spectra for relative quantification of peak pairs formed during fragmentation. Using stringent statistical critera, we identified 48 proteins to be significantly up- or down-regulated, most of which are part of a highly interconnected protein-protein interaction network dominated by proteins involved in translational control. RNA-mediated depletion of a selection of the IR-regulated proteins revealed that the conserved CAR-1/CGH-1/CEY-3 germline RNP complex acts as a novel negative regulator of DNA-damage induced apoptosis. Finally, a central role of nucleolar proteins in orchestrating these responses was confirmed as the H/ACA snRNP protein GAR-1 was required for IR-induced apoptosis in the C. elegans germline.
authors: The Biotechnology Centre of Oslo, University of Oslo, Norway.
authors: Gisele G
authors: GG
authors: Tomazella
authors: Henok
authors: H
authors: Kassahun
authors: Hilde
authors: H
authors: Nilsen
authors: Bernd
authors: B
authors: Thiede
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation / Q000528:radiation effects; D008969:Molecular Sequence Data; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013194:Staining and Labeling; D053719:Tandem Mass Spectrometry
chemical_list: D029742:Caenorhabditis elegans Proteins; D020543:Proteome; D016601:RNA-Binding Proteins