Small nucleolar RNAs U32a, U33, and U35a are critical mediators of metabolic stress

Carlos I. Michel, Christopher L. Holley, Benjamin S. Scruggs, Rohini Sidhu, Rita T. Brookheart, Laura L. Listenberger, Mark A. Behlke, Daniel S. Ory, Jean E. Schaffer

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Lipotoxicity is a metabolic stress response implicated in the pathogenesis of diabetes complications and has been shown to involve lipid-induced oxidative stress. To elucidate the molecular mechanisms of lipotoxicity, we used retroviral promoter trap mutagenesis to isolate a cell line that is resistant to lipotoxic and oxidative stress. We show that loss of three box C/D small nucleolar RNAs (snoRNAs) encoded in the ribosomal protein L13a (rpL13a) locus is sufficient to confer resistance to lipotoxic and oxidative stress in vitro and prevents the propagation of oxidative stress in vivo. Our results provide evidence for a previously unappreciated, non-canonical role for box C/D snoRNAs as regulators of metabolic stress response pathways in mammalian cells.

Original languageEnglish
Pages (from-to)33-44
Number of pages12
JournalCell metabolism
Volume14
Issue number1
DOIs
StatePublished - Jul 6 2011

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