Predicted microRNAs for mammalian circadian rhythms

Area of Science:

• Molecular Biology
• Genetics
• Chronobiology

Background:

• MicroRNAs (miRs) are crucial for posttranscriptional gene regulation.
• Their role in the mammalian circadian clock machinery remains largely unexplored.
• Understanding miR involvement can elucidate novel regulatory mechanisms of circadian rhythms.

Purpose of the Study:

• To identify microRNAs targeting core circadian clock genes.
• To investigate potential feedback loops between miRs and circadian transcription factors.
• To validate the daily expression patterns of candidate miRs in human cells.

Main Methods:

• Utilized predictive bioinformatics analysis to identify conserved miRs targeting mammalian circadian genes.
• Employed three distinct software programs for robust candidate selection.
• Validated daily expression of a candidate microRNA using real-time PCR in human leukocytes.

Main Results:

• Identified 23 known and several novel candidate miRs, including miR-9, miR-24, miR-26, miR-27, miR-93, and miR-302, predicted to target circadian genes.
• Several miRs were predicted to be regulated by key circadian transcription factors (CLOCK/BMAL, DEC2, REV-ERBalpha).
• Demonstrated in vivo daily variation of miR-27b expression in human leukocytes.

Conclusions:

• This study provides predicted feedback loops involving microRNAs in the mammalian molecular clock.
• Presents the first evidence of a microRNA exhibiting daily variation in human tissues.
• Highlights microRNAs as potential regulators of circadian rhythms with implications for chronobiology.