Dicer expression exhibits a tissue-specific diurnal pattern that is lost during aging and in diabetes.
Dysregulation of circadian rhythmicity is identified as a key factor in disease pathogenesis. Circadian rhythmicity is controlled at both a transcriptional and post-transcriptional level suggesting the role of microRNA (miRNA) and double-stranded RNA (dsRNA) in this process. Endonuclease Dicer controls miRNA and dsRNA processing, however the role of Dicer in circadian regulation is not known. Here we demonstrate robust diurnal oscillations of Dicer expression in central and peripheral clock control systems including suprachiasmatic nucleolus (SCN), retina, liver, and bone marrow (BM). The Dicer oscillations were either reduced or phase shifted with aging and Type 2 diabetes. The decrease and phase shift of Dicer expression was associated with a similar decrease and phase shift of miRNAs 146a and 125a-5p and with an increase in toxic Alu RNA. Restoring Dicer levels and the diurnal patterns of Dicer-controlled miRNA and RNA expression may provide new therapeutic strategies for metabolic disease and aging-associated complications.
Genetics and Genomics Graduate Program, University of Florida, Gainesville, Florida, United States of America ; Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida, United States of America ; Genetics Institute, University of Florida, Gainesville, Florida, United States of America.
Yuanqing
Y
Yan
Tatiana E
TE
Salazar
James M
JM
Dominguez
Dung V
DV
Nguyen
Sergio
S
Li Calzi
Ashay D
AD
Bhatwadekar
Xiaoping
X
Qi
Julia V
JV
Busik
Michael E
ME
Boulton
Maria B
MB
Grant
D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020087:Alu Elements / Q000235:genetics; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002940:Circadian Rhythm / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000473:pathology
D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; C534190:Mirn146 microRNA, mouse; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases