LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1
| Autor: | Ken Matsumoto, Mamoru Nagano, Yasufumi Shigeyoshi, Miyuki Shimada, Yoshiyuki Sakaki, Shihoko Kojima, Carla B. Green, Kaoru Saigo, Matsumi Hirose, Hajime Tei, Shin-ichi Hoshino, Kumiko Ui-Tei |
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| Rok vydání: | 2007 |
| Předmět: |
Period (gene)
Molecular Sequence Data Circadian clock Cell Cycle Proteins Biology Mice Biological Clocks Translational regulation Animals Amino Acid Sequence Circadian rhythm Nuclear protein Regulation of gene expression Mice Inbred BALB C Multidisciplinary Suprachiasmatic nucleus Nuclear Proteins RNA-Binding Proteins Period Circadian Proteins Biological Sciences Molecular biology Circadian Rhythm Gene Expression Regulation NIH 3T3 Cells RNA Interference |
| Zdroj: | Proceedings of the National Academy of Sciences. 104:1859-1864 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0607567104 |
| Popis: | The mammalian molecular clock is composed of feedback loops to keep circadian 24-h rhythms. Although much focus has been on transcriptional regulation, it is clear that posttranscriptional controls also play important roles in molecular circadian clocks. In this study, we found that mouse LARK (mLARK), an RNA binding protein, activates the posttranscriptional expression of the mouse Period1 (m Per1 ) mRNA. A strong circadian cycling of the mLARK protein is observed in the suprachiasmatic nuclei with a phase similar to that of mPER1, although the level of the Lark transcripts are not rhythmic. We demonstrate that LARK causes increased mPER1 protein levels, most likely through translational regulation and that the LARK1 protein binds directly to a cis element in the 3′ UTR of the m Per1 mRNA. Alterations of m Lark expression in cycling cells caused significant changes in circadian period, with m Lark knockdown by siRNA resulting in a shorter circadian period, and the overexpression of mLARK1 resulting in a lengthened period. These data indicate that mLARKs are novel posttranscriptional regulators of mammalian circadian clocks. |
| Databáze: | OpenAIRE |
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