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TARANIS interacts with VRILLE and PDP1 to modulate the circadian transcriptional feedback mechanism in Drosophila

Oghenerukevwe Akpoghiran, Dinis J.S. Afonso, Yanan Zhang, View ORCID ProfileKyunghee Koh
doi: https://doi.org/10.1101/2023.05.19.541420
Oghenerukevwe Akpoghiran
1Department of Neuroscience, the Farber Institute for Neurosciences, and Synaptic Biology Center, Thomas Jefferson University, Philadelphia, USA. 19107
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Dinis J.S. Afonso
1Department of Neuroscience, the Farber Institute for Neurosciences, and Synaptic Biology Center, Thomas Jefferson University, Philadelphia, USA. 19107
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Yanan Zhang
1Department of Neuroscience, the Farber Institute for Neurosciences, and Synaptic Biology Center, Thomas Jefferson University, Philadelphia, USA. 19107
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Kyunghee Koh
1Department of Neuroscience, the Farber Institute for Neurosciences, and Synaptic Biology Center, Thomas Jefferson University, Philadelphia, USA. 19107
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  • ORCID record for Kyunghee Koh
  • For correspondence: kyunghee.koh@jefferson.edu
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Abstract

The molecular clock that generates daily rhythms of behavior and physiology consists of interlocked transcription-translation feedback loops. In Drosophila, the primary feedback loop involving the CLOCK-CYCLE transcriptional activators and the PERIOD-TIMELESS transcriptional repressors is interlocked with a secondary loop involving VRILLE (VRI) and PAR DOMAIN PROTEIN 1 (PDP1), a repressor and activator of Clock transcription, respectively. Whereas extensive studies have found numerous transcriptional, translational, and post-translational modulators of the primary loop, relatively little is known about the secondary loop. In this study, we demonstrate that TARANIS (TARA), a Drosophila homolog of the TRIP-Br/SERTAD family of transcriptional coregulators, functions with VRI and PDP1 to modulate the circadian period and rhythm strength in Drosophila. Overexpression of TARA lengthens the circadian period, whereas tara mutants exhibit reduced rhythmicity, a faster molecular clock, and reduced expression of the PDF neuropeptide. We find that TARA can form a physical complex with VRI and PDP1, enhancing their repressor and activator functions, respectively. The conserved SERTA domain of TARA is required to regulate the transcriptional activity of VRI and PDP1, and its deletion leads to reduced locomotor rhythmicity. Consistent with TARA’s role in enhancing VRI and PDP1 activity, overexpressing tara has a similar effect on the circadian period and rhythm strength as simultaneously overexpressing vri and Pdp1. Together, our results suggest that TARA modulates circadian behavior by enhancing the transcriptional activity of VRI and PDP1.

Statement of Significance Internal molecular clocks generating circadian rhythms of around 24 hours broadly impact behavior and physiology, and circadian dysfunction is associated with various neurological and metabolic diseases. The Drosophila circadian clock is a valuable model for understanding the molecular mechanisms underlying daily rhythms. In this study, we identify a conserved gene, taranis, as a novel regulator of the Drosophila molecular clock. We show that TARANIS modulates circadian behavior by physically interacting with and enhancing the transcriptional activity of clock proteins VRILLE and PDP1. Since mammalian homologs of VRILLE and PDP1 also function in the molecular clock, our results have implications for understanding the mammalian circadian clock.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Conflict of Interest Statement: The authors declare no competing financial interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 21, 2023.
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TARANIS interacts with VRILLE and PDP1 to modulate the circadian transcriptional feedback mechanism in Drosophila
Oghenerukevwe Akpoghiran, Dinis J.S. Afonso, Yanan Zhang, Kyunghee Koh
bioRxiv 2023.05.19.541420; doi: https://doi.org/10.1101/2023.05.19.541420
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TARANIS interacts with VRILLE and PDP1 to modulate the circadian transcriptional feedback mechanism in Drosophila
Oghenerukevwe Akpoghiran, Dinis J.S. Afonso, Yanan Zhang, Kyunghee Koh
bioRxiv 2023.05.19.541420; doi: https://doi.org/10.1101/2023.05.19.541420

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