Dicer expression exhibits a tissue-specific diurnal pattern that is lost during aging and in diabetes

Yuanqing Yan, Tatiana E. Salazar, James M. Dominguez, Dung V. Nguyen, Sergio Li Calzi, Ashay D. Bhatwadekar, Xiaoping Qi, Julia V. Busik, Michael E. Boulton, Maria B. Grant

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere80029
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 7 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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