Circadian clock-dependent and -independent posttranscriptional regulation underlies temporal mRNA accumulation in mouse liver

Wang, Jingkui; Symul, Laura; Yeung, Jake; Gobet, Cédric; Sobel, Jonathan; Lück, Sarah; Westermark, Pål O.; Molina, Nacho; Naef, Félix

doi:10.1073/pnas.1715225115

Cited by 69 publications

(90 citation statements)

References 61 publications

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“…This coherent shift most likely represents a cell-cycle defect in the few hepatocytes that underwent through mitosis during the course of the experiment in order to maintain liver homeostasis, as knockdown of condensin II has been shown to lead to extended prometaphase (Green et al, 2012). Most of the other mis-regulated genes have been shown to exhibit a circadian pattern of expression (Fang et al, 2014;Wang et al, 2018). The predominance of circadian genes (defined as gene showing an expression profile varying with at least a 2-fold amplitude during a 24-h period) is highly significant (two-tailed Chi-square test with Yates' correction, P<0.0001).…”

Section: Resultsmentioning

confidence: 99%

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Condensin II inactivation in interphase does not affect chromatin folding or gene expression

Abdennur¹,

Schwarzer

Pękowska

et al. 2018

Preprint

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Condensin complexes have been proposed to play a prominent role in interphase chromatin organization and control of gene expression. Here, we report that the deletion of the central condensin II kleisin subunit Ncaph2 in differentiated mouse hepatocytes does not lead to significant changes in chromosome organization or in gene expression. Both observations challenge current views that implicate condensin in interphase chromosomal domain formation and in enhancer-promoter interactions. Instead, we suggest that the previously reported effects of condensin perturbation may result from their structural role during mitosis, which might indirectly impact the re-establishment of interphase chromosomal architecture after cell division.

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Section: Resultsmentioning

confidence: 99%

“…Peak time and amplitude of circadian variation were taken fromWang et al 2018. Cell cycle data was obtained from Cyclebase v3(Santos et al 2015) Molecular and cellular processes identified by GO-term enrichment analysis.…”

mentioning

confidence: 99%

Condensin II inactivation in interphase does not affect chromatin folding or gene expression

Abdennur¹,

Schwarzer

Pękowska

et al. 2018

Preprint

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“…First, could deadenylation help bridge the circadian rhythm with other rhythmicity? For example, genes related to poly(A) tail regulation, such as Parn, one of the rhythmically expressed deadenylases, are suggested to gain rhythmicity from clock-independent signals (Wang, Symul et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…While rhythmic transcriptional control has been extensively studied, rhythmic control of gene expression also occurs beyond the transcription process (Kojima, Shingle et al 2011, Hirano, Fu et al 2016, Gobet and Naef 2017. Recent genome-wide analyses and mathematical modeling particularly highlighted the role of post-transcriptional regulations in driving rhythmic mRNA expressions , Menet, Rodriguez et al 2012, Luck, Thurley et al 2014, Trott and Menet 2018, Wang, Symul et al 2018. Post-transcriptional regulation targets various processes, such as RNA splicing, nuclear export, cellular translocation, dormancy and degradation of mRNA (Keene 2010).…”

Section: Introductionmentioning

confidence: 99%

Critical role of deadenylation in regulating poly(A) rhythms and circadian gene expression

Yao

Kojima

Chen

2019

Preprint

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AbstractThe mammalian circadian clock is deeply rooted in rhythmic regulation of gene expression. Rhythmic transcriptional control mediated by the circadian transcription factors is thought to be the main driver of mammalian circadian gene expression. However, mounting evidence has demonstrated the importance of rhythmic post-transcriptional controls, and it remains unclear how the transcriptional and post-transcriptional mechanisms collectively control rhythmic gene expression. A recent study discovered rhythmicity in poly(A) tail length in mouse liver and its strong correlation with protein expression rhythms. To understand the role of rhythmic poly(A) regulation in circadian gene expression, we constructed a parsimonious model that depicts rhythmic control imposed upon basic mRNA expression and poly(A) regulation processes, including transcription, deadenylation, polyadenylation, and degradation. The model results reveal the rhythmicity in deadenylation as the strongest contributor to the rhythmicity in poly(A) tail length and the rhythmicity in the abundance of the mRNA subpopulation with long poly(A) tails (a rough proxy for mRNA translatability). In line with this finding, the model further shows that the experimentally observed distinct peak phases in the expression of deadenylases, regardless of other rhythmic controls, can robustly group the rhythmic mRNAs by their peak phases in poly(A) tail length and in abundance of the subpopulation with long poly(A) tails. This provides a potential mechanism to synchronize the phases of target gene expression regulated by the same deadenylases. Our findings highlight the critical role of rhythmic deadenylation in regulating poly(A) rhythms and circadian gene expression.Author SummaryThe biological circadian clock regulates various bodily functions such that they anticipate and respond to the day-and-night cycle. To achieve this, the circadian clock controls rhythmic gene expression, and these genes ultimately drive the rhythmicity of downstream biological processes. As a mechanism of driving circadian gene expression, rhythmic transcriptional control has attracted the central focus. However, mounting evidence has also demonstrated the importance of rhythmic post-transcriptional controls. Here we use mathematical modeling to investigate how transcriptional and post-transcriptional rhythms coordinately control rhythmic gene expression. We have particularly focused on rhythmic regulation of the length of poly(A) tail, a nearly universal feature of mRNAs that controls mRNA stability and translation. Our model reveals that the rhythmicity of deadenylation, the process that shortens the poly(A) tail, is the dominant contributor to the rhythmicity in poly(A) tail length and mRNA translatability. Particularly, the phase of deadenylation nearly overrides the other rhythmic processes in controlling the phases of poly(A) tail length and mRNA translatability. Our finding highlights the critical role of rhythmic deadenylation in circadian gene expression control.

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“…Further, the observed oscillations in NOCT mRNA level necessitate control of mRNA decay in addition to the aforementioned transcriptional control. Indeed, a recent study indicated that NOCT mRNA levels may be regulated by both rhythmic transcription and degradation in mouse liver [80]. Thus far only the liver-specific microRNA miR-122 has been shown to fine-tune the NOCT mRNA abundance profile in mouse liver [81].…”

Section: Noct Expression and Biological Functionsmentioning

confidence: 99%

Regulatory roles of vertebrate Nocturnin: insights and remaining mysteries

2018

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Post-transcriptional control of messenger RNA (mRNA) is an important layer of gene regulation that modulates mRNA decay, translation, and localization. Eukaryotic mRNA decay begins with the catalytic removal of the 3′ poly-adenosine tail by deadenylase enzymes. Multiple deadenylases have been identified in vertebrates and are known to have distinct biological roles; among these proteins is Nocturnin, which has been linked to circadian biology, adipogenesis, osteogenesis, and obesity. Multiple studies have investigated Nocturnin’s involvement in these processes; however, a full understanding of its molecular function remains elusive. Recent studies have provided new insights by identifying putative Nocturnin-regulated mRNAs in mice and by determining the structure and regulatory activities of human Nocturnin. This review seeks to integrate these new discoveries into our understanding of Nocturnin’s regulatory functions and highlight the important remaining unanswered questions surrounding its regulation, biochemical activities, protein partners, and target mRNAs.

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Circadian clock-dependent and -independent posttranscriptional regulation underlies temporal mRNA accumulation in mouse liver

Cited by 69 publications

References 61 publications

Condensin II inactivation in interphase does not affect chromatin folding or gene expression

Condensin II inactivation in interphase does not affect chromatin folding or gene expression

Critical role of deadenylation in regulating poly(A) rhythms and circadian gene expression

Regulatory roles of vertebrate Nocturnin: insights and remaining mysteries

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