title: Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis.
abstract: The RNA exosome is essential for 3' processing of functional RNA species and degradation of aberrant RNAs in eukaryotic cells. Recent reports have defined the substrates of the exosome catalytic domains and solved the multimeric structure of the exosome complex. However, regulation of exosome activity remains poorly characterized, especially in response to physiological stress. Following the observation that cooling of mammalian cells results in a reduction in 40S:60S ribosomal subunit ratio, we uncover regulation of the nuclear exosome as a result of reduced temperature. Using human cells and an in vivo model system allowing whole-body cooling, we observe reduced EXOSC10 (hRrp6, Pm/Scl-100) expression in the cold. In parallel, both models of cooling increase global SUMOylation, leading to the identification of specific conjugation of SUMO1 to EXOSC10, a process that is increased by cooling. Furthermore, we define the major SUMOylation sites in EXOSC10 by mutagenesis and show that overexpression of SUMO1 alone is sufficient to suppress EXOSC10 abundance. Reducing EXOSC10 expression by RNAi in human cells correlates with the 3' preribosomal RNA processing defects seen in the cold as well as reducing the 40S:60S ratio, a previously uncharacterized consequence of EXOSC10 suppression. Together, this work illustrates that EXOSC10 can be modified by SUMOylation and identifies a physiological stress where this regulation is prevalent both in vitro and in vivo.
authors: Medical Research Council Toxicology Unit, Hodgkin Building, Leicester, LE1 9HN, United Kingdom.
authors: John R P
authors: http://orcid.org/0000-0002-8771-5484
authors: JR
authors: Knight
authors: Medical Research Council Toxicology Unit, Hodgkin Building, Leicester, LE1 9HN, United Kingdom.
authors: Amandine
authors: A
authors: Bastide
authors: Medical Research Council Toxicology Unit, Hodgkin Building, Leicester, LE1 9HN, United Kingdom Department of Clinical Neurosciences, Clifford Allbutt Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AH, United Kingdom.
authors: Diego
authors: D
authors: Peretti
authors: Centre for Molecular Processing and School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom.
authors: Anne
authors: A
authors: Roobol
authors: Centre for Molecular Processing and School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom.
authors: Jo
authors: J
authors: Roobol
authors: Medical Research Council Toxicology Unit, Hodgkin Building, Leicester, LE1 9HN, United Kingdom Department of Clinical Neurosciences, Clifford Allbutt Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AH, United Kingdom.
authors: Giovanna R
authors: GR
authors: Mallucci
authors: Centre for Molecular Processing and School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom.
authors: C Mark
authors: CM
authors: Smales
authors: Medical Research Council Toxicology Unit, Hodgkin Building, Leicester, LE1 9HN, United Kingdom.
authors: Anne E
authors: AE
authors: Willis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D058639:Cold-Shock Response; D004794:Enzyme Repression; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism*; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012335:RNA, Ribosomal / Q000378:metabolism; D054683:Ribosome Subunits, Large, Eukaryotic / Q000378:metabolism*; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D058207:Sumoylation
chemical_list: D012335:RNA, Ribosomal; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C077044:EXOSC10 protein, human
keywords: 40S subunits; RNA exosome; SUMOylation; cold shock; rRNA processing