Regulation of a specific circadian clock output pathway by lark, a putative RNA-binding protein with repressor activity

Newby, L M; Jackson, F. Rob

doi:10.1002/(sici)1097-4695(199609)31:1<117::aid-neu10>3.0.co;2-i

Cited by 76 publications

(39 citation statements)

References 53 publications

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“…At the time we began these studies the only protein that contained putative RNA-binding motifs that had been tied to circadian rhythms was Drosophila LARK (dLARK) (22)(23)(24)(25). Using a candidate approach, we decided to investigate a possible role for mammalian Lark homologs in posttranscriptional regulation of mPer1.…”

Section: Resultsmentioning

confidence: 99%

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

Kojima

Matsumoto

Hirose

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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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.circadian rhythms ͉ posttranscriptional regulation ͉ RNA binding protein ͉ 3Јuntranslated region ͉ suprachiasmatic nucleus

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Section: Resultsmentioning

confidence: 99%

“…Using a candidate approach, we decided to investigate a possible role for mammalian Lark homologs in posttranscriptional regulation of mPer1. tion motifs and a CCHC-type zinc finger motif (22)(23)(24)(25)(26)(27) [supporting information (SI) Fig. 7A].…”

Section: Resultsmentioning

confidence: 99%

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

Kojima

Matsumoto

Hirose

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…LARK (or RBM4) is an RNAbinding protein that contains three RNA-binding domains Lai et al, 2003;Newby and Jackson, 1993). In Drosophila, Lark affects locomotor activity and eclosion rhythms (Huang et al, 2009;Newby and Jackson, 1996;Schroeder et al, 2003), and activates the translation of Eip74EF, an ecdysoneinduced protein. The molecular function of Eip74EF has not been clarified, but an Eip74EF mutant fly exhibits an early eclosion phenotype (Huang et al, 2007).…”

Section: Post-transcriptional Regulation In Animalsmentioning

confidence: 99%

Post-transcriptional control of circadian rhythms

Kojima

Shingle

Green

2011

Journal of Cell Science

221

185

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Post-transcriptional regulationThe control of gene expression is a complex process. Even after mRNA is transcribed from DNA, mRNAs can undergo many processing and regulatory steps that influence their expression (Keene, 2010). This type of regulation, at the post-transcriptional level, is beneficial, because it allows cells to alter protein levels rapidly without requiring transcript synthesis or processing. mRNA processing begins immediately following transcription with splicing and, in some cases, results in multiple isoforms of the transcript. Upon translocation into the cytoplasm, some mRNAs directly undergo deadenylation and degradation, whereas others can be stored in cytoplasmic compartments, such as processing bodies or stress granules, until they are degraded or re-polyadenylated. Other transcripts interact with the translational machinery and are translated into protein immediately after localization to the cytoplasm. Other mRNAs interact with localization machinery to Summary Circadian rhythms exist in most living organisms. The general molecular mechanisms that are used to generate 24-hour rhythms are conserved among organisms, although the details vary. These core clocks consist of multiple regulatory feedback loops, and must be coordinated and orchestrated appropriately for the fine-tuning of the 24-hour period. Many levels of regulation are important for the proper functioning of the circadian clock, including transcriptional, post-transcriptional and post-translational mechanisms. In recent years, new information about post-transcriptional regulation in the circadian system has been discovered. Such regulation has been shown to alter the phase and amplitude of rhythmic mRNA and protein expression in many organisms. Therefore, this Commentary will provide an overview of current knowledge of post-transcriptional regulation of the clock genes and clock-controlled genes in dinoflagellates, plants, fungi and animals. This article will also highlight how circadian gene expression is modulated by posttranscriptional mechanisms and how this is crucial for robust circadian rhythmicity.

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“…LARK is an RNA binding protein that is rhythmically expressed in certain neurons of the pupal brain thought to be involved in regulating rhythmic eclosion (McNeil et al, 1998;Zhang et al, 2000). Interestingly, this form of regulation seems to involve only posttranscriptional mechanisms, because lark RNA levels are temporally flat (Newby and Jackson, 1996). Although this is consistent with a function in controlling timed eclosion, the mechanism or downstream targets of LARK are unknown.…”

Section: Mutations Affecting Eclosion Rhythmsmentioning

confidence: 99%

Genetic analysis of the circadian system in Drosophila melanogaster and mammals

2002

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ABSTRACT:The fruit fly, Drosophila melanogaster, has been a grateful object for circadian rhythm researchers over several decades. Behavioral, genetic, and molecular studies helped to reveal the genetic bases of circadian time keeping and rhythmic behaviors. Contrary, mammalian rhythm research until recently was mainly restricted to descriptive and physiologic approaches. As in many other areas of research, the surprising similarity of basic biologic principles between the little fly and our own species, boosted the progress of unraveling the genetic foundation of mammalian clock mechanisms. Once more, not only the basic mechanisms, but also the molecules involved in establishing our circadian system are taken or adapted from the fly. This review will try to give a comparative overview about the two systems, highlighting similarities as well as specifics of both insect and murine clocks.

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Regulation of a specific circadian clock output pathway by lark, a putative RNA-binding protein with repressor activity

Cited by 76 publications

References 53 publications

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

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

Post-transcriptional control of circadian rhythms

Genetic analysis of the circadian system in Drosophila melanogaster and mammals

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