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Rpl13a small nucleolar RNAs regulate systemic glucose metabolism.

Publication ,  Journal Article
Lee, J; Harris, AN; Holley, CL; Mahadevan, J; Pyles, KD; Lavagnino, Z; Scherrer, DE; Fujiwara, H; Sidhu, R; Zhang, J; Huang, SC-C; Piston, DW ...
Published in: J Clin Invest
December 1, 2016

Small nucleolar RNAs (snoRNAs) are non-coding RNAs that form ribonucleoproteins to guide covalent modifications of ribosomal and small nuclear RNAs in the nucleus. Recent studies have also uncovered additional non-canonical roles for snoRNAs. However, the physiological contributions of these small RNAs are largely unknown. Here, we selectively deleted four snoRNAs encoded within the introns of the ribosomal protein L13a (Rpl13a) locus in a mouse model. Loss of Rpl13a snoRNAs altered mitochondrial metabolism and lowered reactive oxygen species tone, leading to increased glucose-stimulated insulin secretion from pancreatic islets and enhanced systemic glucose tolerance. Islets from mice lacking Rpl13a snoRNAs demonstrated blunted oxidative stress responses. Furthermore, these mice were protected against diabetogenic stimuli that cause oxidative stress damage to islets. Our study illuminates a previously unrecognized role for snoRNAs in metabolic regulation.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

December 1, 2016

Volume

126

Issue

12

Start / End Page

4616 / 4625

Location

United States

Related Subject Headings

  • Ribosomal Proteins
  • Reactive Oxygen Species
  • RNA, Small Nuclear
  • Oxidative Stress
  • Mitochondria
  • Mice, Knockout
  • Mice
  • Islets of Langerhans
  • Introns
  • Immunology
 

Citation

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Lee, J., Harris, A. N., Holley, C. L., Mahadevan, J., Pyles, K. D., Lavagnino, Z., … Schaffer, J. E. (2016). Rpl13a small nucleolar RNAs regulate systemic glucose metabolism. J Clin Invest, 126(12), 4616–4625. https://doi.org/10.1172/JCI88069
Lee, Jiyeon, Alexis N. Harris, Christopher L. Holley, Jana Mahadevan, Kelly D. Pyles, Zeno Lavagnino, David E. Scherrer, et al. “Rpl13a small nucleolar RNAs regulate systemic glucose metabolism.J Clin Invest 126, no. 12 (December 1, 2016): 4616–25. https://doi.org/10.1172/JCI88069.
Lee J, Harris AN, Holley CL, Mahadevan J, Pyles KD, Lavagnino Z, et al. Rpl13a small nucleolar RNAs regulate systemic glucose metabolism. J Clin Invest. 2016 Dec 1;126(12):4616–25.
Lee, Jiyeon, et al. “Rpl13a small nucleolar RNAs regulate systemic glucose metabolism.J Clin Invest, vol. 126, no. 12, Dec. 2016, pp. 4616–25. Pubmed, doi:10.1172/JCI88069.
Lee J, Harris AN, Holley CL, Mahadevan J, Pyles KD, Lavagnino Z, Scherrer DE, Fujiwara H, Sidhu R, Zhang J, Huang SC-C, Piston DW, Remedi MS, Urano F, Ory DS, Schaffer JE. Rpl13a small nucleolar RNAs regulate systemic glucose metabolism. J Clin Invest. 2016 Dec 1;126(12):4616–4625.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

December 1, 2016

Volume

126

Issue

12

Start / End Page

4616 / 4625

Location

United States

Related Subject Headings

  • Ribosomal Proteins
  • Reactive Oxygen Species
  • RNA, Small Nuclear
  • Oxidative Stress
  • Mitochondria
  • Mice, Knockout
  • Mice
  • Islets of Langerhans
  • Introns
  • Immunology