Rpl13a small nucleolar RNAs regulate systemic glucose metabolism.
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.
Jiyeon
J
Lee
Alexis N
AN
Harris
Christopher L
CL
Holley
Jana
J
Mahadevan
Kelly D
KD
Pyles
Zeno
Z
Lavagnino
David E
DE
Scherrer
Hideji
H
Fujiwara
Rohini
R
Sidhu
Jessie
J
Zhang
Stanley Ching-Cheng
SC
Huang
David W
DW
Piston
Maria S
MS
Remedi
Fumihiko
F
Urano
Daniel S
DS
Ory
Jean E
JE
Schaffer
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D007438:Introns; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012269:Ribosomal Proteins
D012342:RNA, Small Nuclear; D017382:Reactive Oxygen Species; D012269:Ribosomal Proteins; C520792:Rpl13a protein, mouse; D005947:Glucose