Rpl13a small nucleolar RNAs regulate systemic glucose metabolism
| Autor: | Daniel S. Ory, Maria S. Remedi, Alexis N. Harris, Jean E. Schaffer, Jana Mahadevan, Zeno Lavagnino, Christopher L. Holley, Fumihiko Urano, Hideji Fujiwara, Kelly D. Pyles, David E. Scherrer, Rohini Sidhu, David W. Piston, Stanley Ching-Cheng Huang, Jiyeon Lee, Jessie Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
Ribosomal Proteins
0301 basic medicine Mitochondrion Biology medicine.disease_cause Diabetes Mellitus Experimental Islets of Langerhans Mice 03 medical and health sciences Ribosomal protein RNA Small Nuclear medicine Animals Small nucleolar RNA Ribonucleoprotein Mice Knockout urogenital system Pancreatic islets Intron General Medicine Ribosomal RNA Introns Mitochondria Oxidative Stress Glucose 030104 developmental biology medicine.anatomical_structure Biochemistry Reactive Oxygen Species Oxidative stress Research Article |
| Zdroj: | Journal of Clinical Investigation. 126:4616-4625 |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci88069 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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