PSMD11 modulates circadian clock function through PER and CRY nuclear translocation

Sibel Cal-Kayitmazbatir; Lauren J Francey; Yool Lee; Andrew C Liu; John B Hogenesch

doi:10.1371/journal.pone.0283463

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PSMD11 modulates circadian clock function through PER and CRY nuclear translocation

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PSMD11 modulates circadian clock function through PER and CRY nuclear translocation

Sibel Cal-Kayitmazbatir, Lauren J Francey, Yool Lee, Andrew C Liu and John B Hogenesch

PloS one, Vol.18(3), pp.e0283463-e0283463

03/24/2023

DOI: https://doi.org/10.1371/journal.pone.0283463

PMID: 36961772

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Abstract

ARNTL Transcription Factors - metabolism

Cell Nucleus - metabolism

Circadian Clocks - genetics

Circadian Rhythm - physiology

CLOCK Proteins - genetics

Cryptochromes - genetics

Cryptochromes - metabolism

The molecular circadian clock is regulated by a transcriptional translational feedback loop. However, the post-translational control mechanisms are less understood. The NRON complex is a large ribonucleoprotein complex, consisting of a lncRNA and several proteins. Components of the complex play a distinct role in regulating protein phosphorylation, synthesis, stability, and translocation in cellular processes. This includes the NFAT and the circadian clock pathway. PSMD11 is a component of the NRON complex and a lid component of the 26S proteasome. Among the PSMD family members, PSMD11 has a more specific role in circadian clock function. Here, we used cell and biochemical approaches and characterized the role of PSMD11 in regulating the stability and nuclear translocation of circadian clock proteins. We used size exclusion chromatography to enrich the NRON complex in the cytosolic and nuclear fractions. More specifically, PSMD11 knockdown affected the abundance of PER2 and CRY2 proteins and the nuclear translocation of CRY1. This changed the relative abundance of CRY1 and CRY2 in the nucleus. Thus, this work defines the role of PSMD11 in the NRON complex regulating the nuclear translocation of circadian repressors, thereby enabling cellular circadian oscillations.

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Title: PSMD11 modulates circadian clock function through PER and CRY nuclear translocation
Creators: Sibel Cal-Kayitmazbatir - Cincinnati Children's Hospital Medical Center
Lauren J Francey - Cincinnati Children's Hospital Medical Center
Yool Lee - Washington State University
Andrew C Liu - Department of Physiology and Aging, University of Florida College of Medicine, Gainesville, Florida, United States of America
John B Hogenesch - Cincinnati Children's Hospital Medical Center
Publication Details: PloS one, Vol.18(3), pp.e0283463-e0283463
Academic Unit: Elson S. Floyd College of Medicine
Grant note: R01 NS054794 / NINDS NIH HHS
Identifiers: 99901131064001842
Language: English
Resource Type: Journal article