Post-transcriptional control of circadian rhythms

Department of Neuroscience, University of Texas Southwestern Medical Center, NB4.204G, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Journal of Cell Science (Impact Factor: 5.43). 02/2011; 124(Pt 3):311-20. DOI: 10.1242/jcs.065771
Source: PubMed


Circadian rhythms exist in most living organisms. The general molecular mechanisms that are used to generate 24-hour rhythms are conserved among organisms, although the details vary. These core clocks consist of multiple regulatory feedback loops, and must be coordinated and orchestrated appropriately for the fine-tuning of the 24-hour period. Many levels of regulation are important for the proper functioning of the circadian clock, including transcriptional, post-transcriptional and post-translational mechanisms. In recent years, new information about post-transcriptional regulation in the circadian system has been discovered. Such regulation has been shown to alter the phase and amplitude of rhythmic mRNA and protein expression in many organisms. Therefore, this Commentary will provide an overview of current knowledge of post-transcriptional regulation of the clock genes and clock-controlled genes in dinoflagellates, plants, fungi and animals. This article will also highlight how circadian gene expression is modulated by post-transcriptional mechanisms and how this is crucial for robust circadian rhythmicity.

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Available from: Shihoko Kojima
    • "In addition, endothelial cells dedifferentiate by changing micro-environmental context from in vivo to in vitro condition, losing expression of their tissue-specific genes (Lacorre et al., 2004). Based on the observation that cultivated primary endothelial cells retain a 'cellular memory' of the light/dark condition when donor animals were euthanized (Marçola et al., 2013), and miRNAs are involved in the circadian rhythms control (Staiger and Koster, 2011; Kojima et al., 2011), we hypothesized that these cell cultures, obtained from cremaster muscle, contain undifferentiated cells that express a set of miRNAs imposed by environmental lighting responsible for the regulation of the biological programs involved in the different phenotypes previously observed (Marçola et al., 2013). The most common marker used to distinguish progenitors from mature cells is CD133, also designated prominin-1 (Corbeil et al., 2000; Peichev et al., 2000; Alessandri et al., 2004; Belicchi et al., 2004; Richardson et al., 2004; Bussolati et al., 2005; Torrente et al., 2007; Carter et al., 2009; Cui et al., 2013). "
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    ABSTRACT: The phenotype of primary cells in culture varies according to the donor environmental condition. We recently showed that the time of the day imposes a molecular program linked to the inflammatory response that is heritable in culture. Here we investigated whether microRNAs (miRNAs) would show differential expression according to the time when cells were obtained, namely daytime or nighttime. Cells obtained from explants of cremaster muscle and cultivated until confluence (∼20 days) presented high CD133 expression. Global miRNA expression analysis was performed through deep sequencing in order to compare both cultured cells. A total of 504 mature miRNAs were identified, with a specific miRNA signature being associated to the light versus dark phase of a circadian cycle. miR-1249 and miR-129-2-3p were highly expressed in daytime cells, while miR-182, miR-96-5p, miR-146a-3p, miR-146a-5p and miR-223-3p were highly expressed in nighttime cells. Nighttime cells are regulated for programs involved in cell processes and development, as well as in the inflammation, cell differentiation and maturation; while daytime cells express miRNAs that control stemness and cytoskeleton remodeling. In summary, the time of the day imposes a differential profile regarding to miRNA signature on CD133(+) cells in culture. Understanding this daily profile in the phenotype of cultured cells is highly relevant for clinical outputs, including cellular therapy approaches. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · Journal of Cellular Physiology
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    • "Daily changes in RNA stability , for instance, could account for such rhythms in a way that even though the gene may be transcribed uniformly throughout the day, the stability of the resulting mRNA would change daily and would be detected as a cycling mRNA. This could be mediated, for instance, by specific proteins/noncoding RNAs (ncRNAs) that interact with the target mRNAs and mediate its rhythmic decay (for examples, see Kojima et al., 2011 "
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    ABSTRACT: Circadian clocks drive daily oscillations in a variety of biological processes through the coordinate orchestration of precise gene expression programs. Global expression profiling experiments have suggested that a significant fraction of the transcriptome and proteome is under circadian control, and such output rhythms have historically been assumed to rely on the rhythmic transcription of these genes. Recent genome-wide studies, however, have challenged this long-held view and pointed to a major contribution of posttranscriptional regulation in driving oscillations at the messenger RNA (mRNA) level, while others have highlighted extensive clock translational regulation, regardless of mRNA rhythms. There are various examples of genes that are uniformly transcribed throughout the day but that exhibit rhythmic mRNA levels, and of flat mRNAs, with oscillating protein levels, and such observations have largely been considered to result from independent regulation at each step. These studies have thereby obviated any connections, or coupling, that might exist between the different steps of gene expression and the impact that any of them could have on subsequent ones. Here, we argue that due to both biological and technical reasons, the jury is still out on the determination of the relative contributions of each of the different stages of gene expression in regulating output molecular rhythms. In addition, we propose that through a variety of coupling mechanisms, gene transcription (even when apparently arrhythmic) might play a much relevant role in determining oscillations in gene expression than currently estimated, regulating rhythms at downstream steps. Furthermore, we posit that eukaryotic genomes regulate daily RNA polymerase II (RNAPII) recruitment and histone modifications genome-wide, setting the stage for global nascent transcription, but that tissue-specific mechanisms locally specify the different processes under clock control.
    Full-text · Article · Oct 2015 · Journal of Biological Rhythms
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    • "The expression of most genes is regulated temporally and spatially. Although most of the regulation of gene expression occurs at the transcription step, the regulation of mRNA stability, localization and modulation of translation are crucial steps, particularly in developmental processes (1) and biological clock systems (2–5). Expression profiles of mRNA or protein are not matched in many cases, implying that translational control is a dynamically regulated mechanism, which is not a silent step (6–8). "
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    ABSTRACT: In the present study, we investigated the 3' untranslated region (UTR) of the mouse core clock gene cryptochrome 1 (Cry1) at the post-transcriptional level, particularly its translational regulation. Interestingly, the 3'UTR of Cry1 mRNA decreased its mRNA levels but increased protein amounts. The 3'UTR is widely known to function as a cis-acting element of mRNA degradation. The 3'UTR also provides a binding site for microRNA and mainly suppresses translation of target mRNAs. We found that AU-rich element RNA binding protein 1 (AUF1) directly binds to the Cry1 3'UTR and regulates translation of Cry1 mRNA. AUF1 interacted with eukaryotic translation initiation factor 3 subunit B and also directly associated with ribosomal protein S3 or ribosomal protein S14, resulting in translation of Cry1 mRNA in a 3'UTR-dependent manner. Expression of cytoplasmic AUF1 and binding of AUF1 to the Cry1 3'UTR were parallel to the circadian CRY1 protein profile. Our results suggest that the 3'UTR of Cry1 is important for its rhythmic translation, and AUF1 bound to the 3'UTR facilitates interaction with the 5' end of mRNA by interacting with translation initiation factors and recruiting the 40S ribosomal subunit to initiate translation of Cry1 mRNA.
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