TY - JOUR
T1 - LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1
AU - Kojima, Shihoko
AU - Matsumoto, Ken
AU - Hirose, Matsumi
AU - Shimada, Miyuki
AU - Nagano, Mamoru
AU - Shigeyoshi, Yasufumi
AU - Hoshino, Shin Ichi
AU - Ui-Tei, Kumiko
AU - Saigo, Kaoru
AU - Green, Carla B.
AU - Sakaki, Yoshiyuki
AU - Tei, Hajime
PY - 2007/2/6
Y1 - 2007/2/6
N2 - 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.
AB - 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.
KW - 3′untranslated region
KW - Circadian rhythms
KW - Posttranscriptional regulation
KW - RNA binding protein
KW - Suprachiasmatic nucleus
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U2 - 10.1073/pnas.0607567104
DO - 10.1073/pnas.0607567104
M3 - Article
C2 - 17264215
AN - SCOPUS:33846907098
SN - 0027-8424
VL - 104
SP - 1859
EP - 1864
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -