1. hnRNP K Supports High-Amplitude D Site-Binding Protein mRNA (Dbp mRNA) Oscillation To Sustain Circadian Rhythms
- Author
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Hee Yi, Young Hun Jeong, Sung Wook Kim, Seokjin Ham, Hyo-Min Kim, Hyun-Ok Ku, Paul Kwangho Kwon, Kyong-Tai Kim, Chunghun Lim, Tae-Young Roh, Kyung-Ha Lee, Byunghee Kang, Jung-Hyun Choi, Sookil Tae, and Ji-hyung Kim
- Subjects
0303 health sciences ,Gene knockdown ,Messenger RNA ,Binding protein ,Cell Biology ,Biology ,environment and public health ,Cell biology ,CLOCK ,03 medical and health sciences ,0302 clinical medicine ,Transcription (biology) ,Gene expression ,Heterogeneous-Nuclear Ribonucleoprotein K ,Molecular Biology ,Chromatin immunoprecipitation ,030217 neurology & neurosurgery ,circulatory and respiratory physiology ,030304 developmental biology - Abstract
Circadian gene expression is defined by the gene-specific phase and amplitude of daily oscillations in mRNA and protein levels. D site-binding protein mRNA (Dbp mRNA) shows high-amplitude oscillation; however, the underlying mechanism remains elusive. Here, we demonstrate that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator that activates Dbp transcription via the poly(C) motif within its proximal promoter. Biochemical analyses identified hnRNP K as a specific protein that directly associates with the poly(C) motif in vitro Interestingly, we further confirmed the rhythmic binding of endogenous hnRNP K within the Dbp promoter through chromatin immunoprecipitation as well as the cycling expression of hnRNP K. Finally, knockdown of hnRNP K decreased mRNA oscillation in both Dbp and Dbp-dependent clock genes. Taken together, our results show rhythmic protein expression of hnRNP K and provide new insights into its function as a transcriptional amplifier of Dbp.
- Published
- 2020