KPNB1 mediates PER/CRY nuclear translocation and circadian clock function

ELife
Yool LeeJohn B Hogenesch

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.

References

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Citations

Mar 12, 2016·Biochemical and Biophysical Research Communications·Yang LiEric Erquan Zhang
Oct 1, 2016·Cellular and Molecular Life Sciences : CMLS·Lucia Mendoza-ViverosHai-Ying Mary Cheng
Jan 23, 2020·Journal of Neurogenetics·Christine N SerwayJ Steven de Belle
Nov 8, 2018·The European Journal of Neuroscience·Clark Rosensweig, Carla B Green
May 10, 2020·The FEBS Journal·Sibel Cal-KayitmazbatirIbrahim Halil Kavakli
Oct 11, 2017·Molecular Medicine Reports·Ziqiang ZhangJianjun Du
Oct 28, 2020·Proceedings of the National Academy of Sciences of the United States of America·Stephen BeesleyChoogon Lee
Mar 7, 2021·Genes·Jiapei YanDavid E Somers
Sep 23, 2021·Journal of Biological Rhythms·Yool LeeAmita Sehgal

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Methods Mentioned

BETA
nuclear translocation
Fluorescence
fluorescence imaging microscopy
co-immunoprecipitation
Immunoprecipitation
ChIP
fluorescence microscopy
transfection
transgenic
PCR

Software Mentioned

ImageJ
ClockLab
WaveClock
pdf - GS )
pdf Gene Switch (
Actimetrics

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