IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
STRESS GRANULES CONTROL PROTEIN SYNTHESIS AND HAVE A NOVEL LINK TO NEURODEGENERATION
Autor/es:
MAXIMILIANO J KATZ; MARCELO PÉREZ; GRACIELA LIDIA BOCCACCIO; PABLO WAPPNER
Lugar:
Córdoba, Córdoba
Reunión:
Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
Stress granules (SGs) are cytoplasmic supramolecular aggregates that form transiently in eukaryote cells upon acute stress. SGs belong to a growing family of ?liquid organelles?, which are membraneless and depend on protein aggregation domains for their formation. SGs contain repressed mRNAs, translation initiation factors and several RNA-binding proteins and are related to a number of abnormal protein aggregates present in neurodegeneration. Their significance to cell survival remains elusive. Here we show that SGs are involved in the control of the translational reprogramming upon stress. Using a puromycin-based method to measure translation in single cells we found that SGs form after the shutdown of protein synthesis and inactivation of eIF2alpha. However, the recovery of translation correlates with SG dissolution, thus suggesting that SG disassembly and release of mRNAs might be an important event to reinitiate protein synthesis. In a RNAi?based screen performed in Drosophila cells we identified 21 positive and 16 negative modulators of SG formation involved in mRNA metabolism and translation and linked to neurodegeneration. We confirmed the role of the vertebrate homologs in mammalian cell lines and we are currently investigating their role in the neuronal stress response in the Drosophila brain.We thank the DRSC, HMS, and ANPCyT, CONICET and UBA, Argentina for funding.