Rhythmic post-transcriptional regulation of the circadian clock protein mPER2 in mammalian cells: a real-time analysis.
Post-transcriptional/translational mechanisms regulate the circadian clock system of many organisms, including mammals. The level of the essential clock protein mPER2 daily oscillates in peripheral cells as well as in neurons of the master oscillator in the suprachiasmatic nucleus (SCN). Post-translational modifications of mPER2, such as phosphorylation and ubiquitination, are likely involved in the regulation of its stability and intracellular accumulation rhythms, which in turn create an approximately 2-4 h delay from the rhythm of mPer2 mRNA. However, there are no direct evidences linking the above biochemical processes to the generation of the mPER2 protein cycle itself. Here, we show that multiple circadian waves of bioluminescence are detectable in cells constitutively expressing an mPer2-luciferase fusion mRNA. This suggests that a post-transcriptional/translational mechanism itself is capable of generating the circadian mPER2 accumulation cycle, and thus this type of regulation may function in the circadian clock system in mammals.
COE Unit of Circadian System, Nagoya University Graduate School of Science, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
Keigo
K
Nishii
Iori
I
Yamanaka
Maya
M
Yasuda
Yota B
YB
Kiyohara
Yoko
Y
Kitayama
Takao
T
Kondo
Kazuhiro
K
Yagita
D000818:Animals; D001681:Biological Assay / Q000379:methods; D001683:Biological Clocks / Q000235:genetics*; D018797:Cell Cycle Proteins; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D056950:Period Circadian Proteins; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D018797:Cell Cycle Proteins; D008164:Luminescent Proteins; D009687:Nuclear Proteins; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D008156:Luciferases