title: LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1.
abstract: 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 (mPer1) 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 mPer1 mRNA. Alterations of mLark expression in cycling cells caused significant changes in circadian period, with mLark 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.
authors.affiliation: Laboratory of Chronogenomics, Mitsubishi Kagaku Institute of Life Sciences, Minamiooya, Machida, Tokyo, Japan.
authors.forename: Shihoko
authors.initials: S
authors.lastname: Kojima
authors.forename: Ken
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Matsumi
authors.initials: M
authors.lastname: Hirose
authors.forename: Miyuki
authors.initials: M
authors.lastname: Shimada
authors.forename: Mamoru
authors.initials: M
authors.lastname: Nagano
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Shigeyoshi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hoshino
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ui-Tei
authors.forename: Kaoru
authors.initials: K
authors.lastname: Saigo
authors.forename: Carla B
authors.initials: CB
authors.lastname: Green
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakaki
authors.forename: Hajime
authors.initials: H
authors.lastname: Tei
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics*; D056950:Period Circadian Proteins; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C518159:LARK protein, mouse; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D016601:RNA-Binding Proteins