A bioinformatic analysis identifies circadian expression of splicing factors and time-dependent alternative splicing events in the HD-MY-Z cell line

Genov, Nikolai; Basti, Alireza; Abreu, Marconi; Astaburuaga, Rosario; Relógio, Angela

doi:10.1038/s41598-019-47343-w

Cited by 13 publications

(12 citation statements)

References 90 publications

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“…While the 8-h gene set showed an enrichment of terms related to metabolism, the 12-h set showed an enrichment of terms related to endoplasmic reticulum (ER)-related processes, splicing, translation and gene expression regulation. The 24-h rhythmically expressed genes showed an enrichment of terms related to meiosis, and splicing (Figure S3), which is in line with our previous findings [25,26,27,28].…”

Section: Resultssupporting

confidence: 91%

A Multi-Layered Study on Harmonic Oscillations in Mammalian Genomics and Proteomics

Genov

Castellana

Scholkmann

et al. 2019

IJMS

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Cellular, organ, and whole animal physiology show temporal variation predominantly featuring 24-h (circadian) periodicity. Time-course mRNA gene expression profiling in mouse liver showed two subsets of genes oscillating at the second (12-h) and third (8-h) harmonic of the prime (24-h) frequency. The aim of our study was to identify specific genomic, proteomic, and functional properties of ultradian and circadian subsets. We found hallmarks of the three oscillating gene subsets, including different (i) functional annotation, (ii) proteomic and electrochemical features, and (iii) transcription factor binding motifs in upstream regions of 8-h and 12-h oscillating genes that seemingly allow the link of the ultradian gene sets to a known circadian network. Our multifaceted bioinformatics analysis of circadian and ultradian genes suggests that the different rhythmicity of gene expression impacts physiological outcomes and may be related to transcriptional, translational and post-translational dynamics, as well as to phylogenetic and evolutionary components.

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Section: Resultssupporting

confidence: 91%

A Multi-Layered Study on Harmonic Oscillations in Mammalian Genomics and Proteomics

Genov

Castellana

Scholkmann

et al. 2019

IJMS

Self Cite

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“…For some time now, evidence has been accumulating pointing to the fact that AS can affect clock components and, that mutations affecting spliceosome related components can alter the circadian period (12,13,16,17,44). Furthermore, studies performed in fruit flies, mice and human cell lines have identified a role for the circadian clock in the control of the splicing process (45-47). Yet there have been no global transcriptomic studies that allowed for understanding the extent of clock control on AS on any plant species.…”

Section: Discussionmentioning

confidence: 99%

Global transcriptome analysis reveals circadian control of splicing events in Arabidopsis thaliana

Romanowski

Schlaen

Perez-Santángelo

et al. 2019

Preprint

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SUMMARYThe circadian clock of Arabidopsis thaliana controls many physiological and molecular processes, allowing plants to anticipate daily changes in their environment. However, developing a detailed understanding of how oscillations in mRNA levels are connected to oscillations in post-transcriptional processes, such as splicing, has remained a challenge.Here we applied a combined approach using deep transcriptome sequencing and bioinformatics tools to identify novel circadian regulated genes and splicing events.Using a stringent approach, we identified 300 intron retention, 8 exon skipping, 79 alternative 3’ splice site usage, 48 alternative 5’ splice site usage, and 350 multiple (more than one event type) annotated events under circadian regulation. We also found 7 and 721 novel alternative exonic and intronic events. Depletion of the circadian regulated splicing factor AtSPF30 homolog, resulted in the disruption of a subset of clock controlled splicing events.Altogether, our global circadian RNA-seq coupled with an in silico, event centred, splicing analysis tool offers a new approach for studying the interplay between the circadian clock and the splicing machinery at a global scale. The identification of many circadian regulated splicing events broadens our current understanding of the level of control that the circadian clock has over this posttranscriptional regulatory layer.

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“…Recent studies have also found that splicing-related genes have temporal expression patterns that oscillate every 24 h [90][91][92]. Alternative splicing of U2-auxiliary-factor 26 has been shown to destabilize PER1 in mice [90].…”

Section: Mutations Epigenetic Changes and Deregulated Expression Of mentioning

confidence: 99%

The Cancer Clock Is (Not) Ticking: Links between Circadian Rhythms and Cancer

et al. 2019

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Circadian rhythms regulate many physiological and behavioral processes, including sleep, metabolism and cell division, which have a 24-h oscillation pattern. Rhythmicity is generated by a transcriptional–translational feedback loop in individual cells, which are synchronized by the central pacemaker in the brain and external cues. Epidemiological and clinical studies indicate that disruption of these rhythms can increase both tumorigenesis and cancer progression. Environmental changes (shift work, jet lag, exposure to light at night), mutations in circadian regulating genes, and changes to clock gene expression are recognized forms of disruption and are associated with cancer risk and/or cancer progression. Experimental data in animals and cell cultures further supports the role of the cellular circadian clock in coordinating cell division and DNA repair, and disrupted cellular clocks accelerate cancer cell growth. This review will summarize studies linking circadian disruption to cancer biology and explore how such disruptions may be further altered by common characteristics of tumors including hypoxia and acidosis. We will highlight how circadian rhythms might be exploited for cancer drug development, including how delivery of current chemotherapies may be enhanced using chronotherapy. Understanding the role of circadian rhythms in carcinogenesis and tumor progression will enable us to better understand causes of cancer and how to treat them.

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A bioinformatic analysis identifies circadian expression of splicing factors and time-dependent alternative splicing events in the HD-MY-Z cell line

Cited by 13 publications

References 90 publications

A Multi-Layered Study on Harmonic Oscillations in Mammalian Genomics and Proteomics

A Multi-Layered Study on Harmonic Oscillations in Mammalian Genomics and Proteomics

Global transcriptome analysis reveals circadian control of splicing events in Arabidopsis thaliana

The Cancer Clock Is (Not) Ticking: Links between Circadian Rhythms and Cancer

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