Abstract
Circadian rhythm is an autoregulatory rhythm, which is sustained by various mechanisms. The nucleocytoplasmic shuttling of BMAL1 is essential for CLOCK translocation between cytoplasm and nucleus and maintenance of the correct pace of the circadian clock. Here we showed that RAE1 and NUP98 can promote the degradation of BMAL1 and CLOCK. Knockdown of RAE1 and NUP98 suppressed BMAL1 shuttling, leading to cytoplasm accumulation of CLOCK. Furthermore, Chip assay showed that knockdown of RAE1 and NUP98 can enhance the interaction between CLOCK: BMAL1 and E-box region in the promoters of Per2 and Cry1 while reducing its transcription activation activity. Our present study firstly revealed that RAE1 and NUP98 are critical regulators for BMAL1 shuttling.
Highlights
Circadian rhythm is a biological rhythm governing physiology and behavior with a period of 24 h that runs in tight synchrony with environmental cues, such as light and temperature[1]
The results showed that exogenous RAE1-HA can directly bind with CLOCKFLAG and BMAL1-FLAG, but NUP98-HA can only bind with CLOCK-FLAG (Fig. 1b)
Immunofluorescence assays showed that the endogenous RAE1, CLOCK, and BMAL1 in NIH3T3 cells were mainly overlapped in the nucleus
Summary
Circadian rhythm is a biological rhythm governing physiology and behavior with a period of 24 h that runs in tight synchrony with environmental cues, such as light and temperature[1]. Circadian clocks are based on cellautonomous and autoregulatory rhythm, which is generated by transcription–translation feedback loops[3,4]. In this model, the heterodimeric transcriptional activators BMAL1 and CLOCK that contain bHLH and PAS domains promote the transcription of CACGTG E-box or E-box-like containing clock-controlled genes (CCGs), such as Cryptochrome (Cry1-2) and Period (Per1-3) genes[5,6,7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
