microRNA modulation of circadian-clock period and entrainment.
microRNAs (miRNAs) are a class of small, noncoding RNAs that regulate the stability or translation of mRNA transcripts. Although recent work has implicated miRNAs in development and in disease, the expression and function of miRNAs in the adult mammalian nervous system have not been extensively characterized. Here, we examine the role of two brain-specific miRNAs, miR-219 and miR-132, in modulating the circadian clock located in the suprachiasmatic nucleus. miR-219 is a target of the CLOCK and BMAL1 complex, exhibits robust circadian rhythms of expression, and the in vivo knockdown of miR-219 lengthens the circadian period. miR-132 is induced by photic entrainment cues via a MAPK/CREB-dependent mechanism, modulates clock-gene expression, and attenuates the entraining effects of light. Collectively, these data reveal miRNAs as clock- and light-regulated genes and provide a mechanistic examination of their roles as effectors of pacemaker activity and entrainment.
Cheng
Hai-Ying M
HY
Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA. hymcheng@yahoo.ca
Papp
Joseph W
JW
Varlamova
Olga
O
Dziema
Heather
H
Russell
Brandon
B
Curfman
John P
JP
Nakazawa
Takanobu
T
Shimizu
Kimiko
K
Okamura
Hitoshi
H
Impey
Soren
S
Obrietan
Karl
K
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001683:Biological Clocks / Q000235:genetics* / Q000528:radiation effects; D001923:Brain Chemistry / Q000235:genetics*; D056926:CLOCK Proteins; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics* / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000528:radiation effects; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010775:Photic Stimulation; D017440:Photoperiod; D013493:Suprachiasmatic Nucleus / Q000033:anatomy & histology / Q000378:metabolism* / Q000528:radiation effects; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000528:radiation effects
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C538943:CLOCK protein, human; C538944:Clock protein, mouse