Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis

John R.P. Knight, Amandine Bastide, Diego Peretti, Anne Roobol, Jo Roobol, Giovanna R. Mallucci, C. Mark Smales, Anne E. Willis

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)623-635
Number of pages13
JournalRNA
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 2016

Keywords

  • 40S subunits
  • Cold shock
  • RNA exosome
  • RRNA processing
  • SUMOylation

Fingerprint

Dive into the research topics of 'Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis'. Together they form a unique fingerprint.

Cite this