hnrnp k supports high-amplitude d site-binding protein mrna (dbp mrna) oscillation to sustain circadian rhythms

Paul Kwangho Kwon; Kyung Ha Lee; Ji Hyung Kim; Sookil Tae; Seokjin Ham; Young Hun Jeong; Sung Wook Kim; Byunghee Kang; Hyo Min Kim; Jung Hyun Choi; Hee Yi; Hyun Ok Ku; Tae Young Roh; Chunghun Lim; Kyong Tai Kim

doi:10.1128/MCB.00537-19

hnrnp k supports high-amplitude d site-binding protein mrna (dbp mrna) oscillation to sustain circadian rhythms

Paul Kwangho Kwon, Kyung Ha Lee, Ji Hyung Kim, Sookil Tae, Seokjin Ham, Young Hun Jeong, Sung Wook Kim, Byunghee Kang, Hyo Min Kim, Jung Hyun Choi, Hee Yi, Hyun Ok Ku, Tae Young Roh, Chunghun Lim, Kyong Tai Kim

Life Sciences

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English
Article number	e00537-19
Journal	Molecular and Cellular Biology
Volume	40
Issue number	6
DOIs	https://doi.org/10.1128/MCB.00537-19
State	Published - 2020

Bibliographical note

Funding Information:
This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (no. 2017M3C7A1023478), by the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (no. 2019R1A2C2009440), by the Cooperative Research Program for Agriculture Science & Technology Development (project no. PJ01324801) of the Rural Development Administration, and by BK21 Plus funded by the Ministry of Education, Republic of Korea (10Z20130012243). We declare no conflict of interest.

Publisher Copyright:
© 2020 American Society for Microbiology.

Keywords

Circadian rhythm
Dbp
HnRNP K
MRNA oscillation

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10.1128/MCB.00537-19

Cite this

Kwon, P. K., Lee, K. H., Kim, J. H., Tae, S., Ham, S., Jeong, Y. H., Kim, S. W., Kang, B., Kim, H. M., Choi, J. H., Yi, H., Ku, H. O., Roh, T. Y., Lim, C., & Kim, K. T. (2020). hnrnp k supports high-amplitude d site-binding protein mrna (dbp mrna) oscillation to sustain circadian rhythms. Molecular and Cellular Biology, 40(6), Article e00537-19. https://doi.org/10.1128/MCB.00537-19

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title = "hnrnp k supports high-amplitude d site-binding protein mrna (dbp mrna) oscillation to sustain circadian rhythms",

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.",

keywords = "Circadian rhythm, Dbp, HnRNP K, MRNA oscillation",

author = "Kwon, {Paul Kwangho} and Lee, {Kyung Ha} and Kim, {Ji Hyung} and Sookil Tae and Seokjin Ham and Jeong, {Young Hun} and Kim, {Sung Wook} and Byunghee Kang and Kim, {Hyo Min} and Choi, {Jung Hyun} and Hee Yi and Ku, {Hyun Ok} and Roh, {Tae Young} and Chunghun Lim and Kim, {Kyong Tai}",

note = "Funding Information: This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (no. 2017M3C7A1023478), by the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (no. 2019R1A2C2009440), by the Cooperative Research Program for Agriculture Science & Technology Development (project no. PJ01324801) of the Rural Development Administration, and by BK21 Plus funded by the Ministry of Education, Republic of Korea (10Z20130012243). We declare no conflict of interest. Publisher Copyright: {\textcopyright} 2020 American Society for Microbiology.",

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doi = "10.1128/MCB.00537-19",

language = "English",

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AU - Kwon, Paul Kwangho

AU - Lee, Kyung Ha

AU - Kim, Ji Hyung

AU - Tae, Sookil

AU - Ham, Seokjin

AU - Jeong, Young Hun

AU - Kim, Sung Wook

AU - Kang, Byunghee

AU - Kim, Hyo Min

AU - Choi, Jung Hyun

AU - Yi, Hee

AU - Ku, Hyun Ok

AU - Roh, Tae Young

AU - Lim, Chunghun

AU - Kim, Kyong Tai

N1 - Funding Information: This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (no. 2017M3C7A1023478), by the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (no. 2019R1A2C2009440), by the Cooperative Research Program for Agriculture Science & Technology Development (project no. PJ01324801) of the Rural Development Administration, and by BK21 Plus funded by the Ministry of Education, Republic of Korea (10Z20130012243). We declare no conflict of interest. Publisher Copyright: © 2020 American Society for Microbiology.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Circadian rhythm

KW - Dbp

KW - HnRNP K

KW - MRNA oscillation

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DO - 10.1128/MCB.00537-19

M3 - Article

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AN - SCOPUS:85080831832

SN - 0270-7306

VL - 40

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 6

M1 - e00537-19

ER -

hnrnp k supports high-amplitude d site-binding protein mrna (dbp mrna) oscillation to sustain circadian rhythms

Abstract

Bibliographical note

Keywords

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