LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1

Shihoko Kojima, Ken Matsumoto, Matsumi Hirose, Miyuki Shimada, Mamoru Nagano, Yasufumi Shigeyoshi, Shin Ichi Hoshino, Kumiko Ui-Tei, Kaoru Saigo, Carla B. Green, Yoshiyuki Sakaki, Hajime Tei

Research output: Contribution to journalArticle

74 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1859-1864
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number6
DOIs
StatePublished - Feb 6 2007

Keywords

  • 3′untranslated region
  • Circadian rhythms
  • Posttranscriptional regulation
  • RNA binding protein
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • General

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    Kojima, S., Matsumoto, K., Hirose, M., Shimada, M., Nagano, M., Shigeyoshi, Y., Hoshino, S. I., Ui-Tei, K., Saigo, K., Green, C. B., Sakaki, Y., & Tei, H. (2007). LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1. Proceedings of the National Academy of Sciences of the United States of America, 104(6), 1859-1864. https://doi.org/10.1073/pnas.0607567104