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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Michel, CI; Holley, CL; Scruggs, BS; Sidhu, R; Brookheart, RT; Listenberger, LL; Behlke, MA; Ory, DS; Schaffer, JE

Published Date

  • July 2011

Published In

Volume / Issue

  • 14 / 1

Start / End Page

  • 33 - 44

PubMed ID

  • 21723502

Pubmed Central ID

  • 21723502

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2011.04.009

Language

  • eng