Distinct roles of DBHS family members in the circadian transcriptional feedback loop
- Kowalska, Elzbieta Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
- Ripperger, Jürgen A. Department of Biology, Unit for Biochemistry, University of Fribourg, Switzerland
- Muheim, Christine Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
- Maier, Bert Laboratory of Chronobiology, Institute of Medical Immunology, Charite Universitätsmedizin, Berlin, Germany
- Kurihara, Yasuyuki Department of Natural Environment and Information, Yokohama National University, Japan
- Fox, Archa H. Western Australian Institute for Medical Research and Centre For Medical Research, University of Western Australia, Crawley Australia
- Kramer, Achim Laboratory of Chronobiology, Institute of Medical Immunology, Charite Universitätsmedizin, Berlin, Germany
- Brown, Steven A. Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
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10.09.2012
Published in:
- Molecular and Cellular Biology. - 2012, vol. 32, no. 22, p. 4585-4594
English
Factors interacting with core circadian clock components are essential to achieve transcriptional feedback necessary for metazoan clocks. Here we show that all three members of the Drosophila Behavior Human Splicing (DBHS) family of RNA-binding proteins play a role in the mammalian circadian oscillator, abrogating or altering clock function when overexpressed or depleted in cells. Although these proteins are members of so-called nuclear paraspeckles, depletion of paraspeckles themselves via silencing of the structural non-coding RNA (ncRNA) Neat1 did not affect overall clock function, suggesting that paraspeckles are not required for DBHS-mediated circadian effects. Instead, we show that the proteins bound to circadian promoter DNA in a fashion that required the PERIOD (PER) proteins, and potently repressed E box-mediated transcription but not CMV promoter-mediated transcription when exogenously recruited. Nevertheless, mice with one or both copies of these genes deleted show only small changes in period length or clock gene expression in vivo. Data from transient transfections show that each of these proteins can either repress or activate depending on the context. Taken together, our data suggest that all of the DBHS family members serve overlapping or redundant roles as transcriptional cofactors at circadian clock-regulated genes.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 30457
- DOI 10.1128/MCB.00334-12
- Persistent URL
- https://folia.unifr.ch/unifr/documents/302731
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