title: The sirtuin SIRT6 regulates stress granule formation in C. elegans and mammals.
abstract: SIRT6 is a NAD(+)-dependent deacetylase that modulates chromatin structure and safeguards genomic stability. Until now, SIRT6 has been assigned to the nucleus and only nuclear targets of SIRT6 are known. Here, we demonstrate that in response to stress, C. elegans SIR-2.4 and its mammalian orthologue SIRT6 localize to cytoplasmic stress granules, interact with various stress granule components and induce their assembly. Loss of SIRT6 or inhibition of its catalytic activity in mouse embryonic fibroblasts impairs stress granule formation and delays disassembly during recovery, whereas deficiency of SIR-2.4 diminishes maintenance of P granules and decreases survival of C. elegans under stress conditions. Our findings uncover a novel, evolutionary conserved function of SIRT6 in the maintenance of stress granules in response to stress.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Epigenetics in C. elegans group, Am Faßberg 11, 37077 Göttingen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Jedrusik-Bode
authors.forename: Maja
authors.initials: M
authors.lastname: Studencka
authors.forename: Christian
authors.initials: C
authors.lastname: Smolka
authors.forename: Tobias
authors.initials: T
authors.lastname: Baumann
authors.forename: Henning
authors.initials: H
authors.lastname: Schmidt
authors.forename: Jan
authors.initials: J
authors.lastname: Kampf
authors.forename: Franziska
authors.initials: F
authors.lastname: Paap
authors.forename: Sophie
authors.initials: S
authors.lastname: Martin
authors.forename: Jamal
authors.initials: J
authors.lastname: Tazi
authors.forename: Kristian M
authors.initials: KM
authors.lastname: Müller
authors.forename: Marcus
authors.initials: M
authors.lastname: Krüger
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.forename: Eva
authors.initials: E
authors.lastname: Bober
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure; D002843:Chromatin / Q000235:genetics*; D003594:Cytoplasmic Granules / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D042822:Genomic Instability; D008322:Mammals; D051379:Mice; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D002843:Chromatin; C501860:Sirt6 protein, mouse; D037761:Sirtuins
keywords: C. elegans; G3BP; SIRT6; Sirtuins; Stress; Stress granules