Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Chemical screen for clock shifter compounds.
  • Fig. S2. BioDare2 analyses of the various nucleotides including cordycepin for the clock effect.
  • Fig. S3. Cordycepin hijacks the adenosine metabolism pathways to shift circadian phase.
  • Fig. S4. Cordycepin regulates the clock phase in the tissue explants.
  • Fig. S5. Cordycepin penetrates through the BBB but degrades quickly in the rodent brain.
  • Fig. S6. The phase shift of cordycepin in mouse locomotor depends on the time of its administration.
  • Fig. S7. Combined approaches reveal RUVBL2 as the target of cordycepin in regulating the clock phase.
  • Fig. S8. Knockdown efficiency of RUVBL2 in U2OS cells.
  • Fig. S9. Rhythmic expression of RUVBL2 in the SCN.
  • Fig. S10. Two mouse Ruvbl genes are rhythmically expressed in vivo.
  • Fig. S11. TIP60 complex is likely involved in the clock regulation.
  • Fig. S12. The PAQosome complex may not be involved in the clock regulation.
  • Fig. S13. Cell lines and the BMAL1 coimmunoprecipitation assays.
  • Fig. S14. Structural analysis of RUVBL ATPases and phosphorylated cordycepin.
  • Fig. S15. Pharmacokinetic analyses of cordycepin and CoTP in U2OS cells.
  • Fig. S16. Physical interactions between RUVBL2 proteins and CoTP/ATP.
  • Fig. S17. Cordycepin induces the expression of E-box genes in vivo.
  • Fig. S18. The PAQosome complex may not be present in the circadian super-complex.
  • Fig. S19. Cordycepin disrupts the interaction between RUVBL2 and BMAL1.
  • Fig. S20. Cartoon of the proposed megadalton circadian repressive super-complex on an E-box containing clock gene.
  • References (5162)

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (Microsoft Excel format). Phase responsive curve of the cordycepin treatment analyzed by BioDare2.
  • Data file S2 (Microsoft Excel format). Cotreatment of pentostatin and cordycepin analyzed by BioDare2.
  • Data file S3 (Microsoft Excel format). siRNA screen targets responsible for the cordycepin treatment effect.
  • Data file S4 (Microsoft Excel format). IP-MS to identify the biotinylated cordycepin-bound proteins.
  • Data file S5 (Microsoft Excel format). IP-MS to identify the megadalton super-complex components via BN-PAGE.
  • Data file S6 (Microsoft Excel format). Statistics of crystallization data collection and structure refinement.
  • Data file S7 (Microsoft Excel format). Primers used for RT-PCR/qPCR.
  • Data file S8 (Microsoft Excel format). All digital data used for generating figures.