KPNB1 mediates PER/CRY nuclear translocation and circadian clock function
Abstract
Regulated nuclear translocation of the PER/CRY repressor complex is critical for negative feedback regulation of the circadian clock of mammals. However, the precise molecular mechanism is not fully understood. Here, we report that KPNB1, an importin β component of the ncRNA repressor of nuclear factor of activated T cells (NRON) ribonucleoprotein complex, mediates nuclear translocation and repressor function of the PER/CRY complex. RNAi depletion of KPNB1 traps the PER/CRY complex in the cytoplasm by blocking nuclear entry of PER proteins in human cells. KPNB1 interacts mainly with PER proteins and directs PER/CRY nuclear transport in a circadian fashion. Interestingly, KPNB1 regulates the PER/CRY nuclear entry and repressor function, independently of importin α, its classical partner. Moreover, inducible inhibition of the conserved Drosophila importin β in lateral neurons abolishes behavioral rhythms in flies. Collectively, these data show that KPNB1 is required for timely nuclear import of PER/CRY in the negative feedback regulation of the circadian clock.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 29, 2015
- Source ID
- 10.7554/elife.08647
Entities
People
- A Reum Jang
- Amita Sehgal
- John B. Hogenesch
- Lauren J. Francey
- Yool Lee
Organizations
- Defense Advanced Research Projects Agency
- National Institute of Neurological Disorders and Stroke
- Pennsylvania Department of Health
- University of Pennsylvania