Identification and Characterization of Transcripts Regulated by Circadian Alternative Polyadenylation in Mouse Liver

Gendreau, Kerry L.; Unruh, Benjamin A; Zhou, Chuanli; Kojima, Shihoko

doi:10.1534/g3.118.200559

Cited by 21 publications

(18 citation statements)

References 86 publications

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“…In addition to AS, we identified genome-wide rhythmicity of APA in Arabidopsis, that has been previously reported in mouse liver (48). Interestingly, APA-related and AS-related genes oscillated in a similar pattern, implying that the factors of two different posttranscriptional mechanisms are synchronized by the circadian clock in a similar way.…”

Section: Discussionsupporting

confidence: 65%

The circadian clock shapes the Arabidopsis transcriptome by regulating alternative splicing and alternative polyadenylation

Yang

Sancar

et al. 2020

Journal of Biological Chemistry

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The circadian clock in plants temporally coordinates biological processes throughout the day, synchronizing gene expression with diurnal environmental changes. Circadian oscillator proteins are known to regulate the expression of clock-controlled plant genes by controlling their transcription. Here, using a high-throughput RNA-Seq approach, we examined genome-wide circadian and diurnal control of the Arabidopsis transcriptome, finding that the oscillation patterns of different transcripts of multitranscript genes can exhibit substantial differences and demonstrating that the circadian clock affects posttranscriptional regulation. In parallel, we found that two major posttranscriptional mechanisms, alternative splicing (AS; especially intron retention) and alternative polyadenylation (APA), display circadian rhythmicity resulting from oscillation in the genes involved in AS and APA. Moreover, AS-related genes exhibited rhythmic AS and APA regulation, adding another layer of complexity to circadian regulation of gene expression. We conclude that the Arabidopsis circadian clock not only controls transcription of genes but also affects their posttranscriptional regulation by influencing alternative splicing and alternative polyadenylation.

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Section: Discussionsupporting

confidence: 65%

The circadian clock shapes the Arabidopsis transcriptome by regulating alternative splicing and alternative polyadenylation

Yang

Sancar

et al. 2020

Journal of Biological Chemistry

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“…Recently, many transcripts have been shown to exhibit circadian oscillations in 3' UTR length (Gendreau et al (2018); Greenwell et al (2020); Yang et al (2020)). It would be interesting to find out in future studies whether and to what extent the rhythmicity in 3' UTR length a↵ects the mechanisms of temperature compensation.…”

Section: Discussionmentioning

confidence: 99%

An integrative omics approach reveals posttranscriptional mechanisms underlying circadian temperature compensation

Schmal

Maier

Ashwal-Fluss

et al. 2021

Preprint

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A defining property of circadian clocks is temperature compensation, characterized by the resilience of circadian free-running periods against changes in environmental temperature. As an underlying mechanism, the balance or critical reaction hypothesis have been proposed. While the former supposes a temperature-dependent balancing of reactions with opposite effects on circadian period, the latter assumes an insensitivity of certain critical period determining regulations upon temperature changes. Posttranscriptional regulations such as temperature-sensitive alternative splicing or phosphorylation have been described as underlying reactions. Here, we show that knockdown of cleavage and polyadenylation specificity factor subunit 6 (CPSF6), a key regulator of 3'-end cleavage and polyadenylation, abolishes circadian temperature compensation in U-2 OS cells. We apply a combination of 3'-End-RNA-seq and mass spectrometry-based proteomics to globally quantify changes in 3' UTR length as well as gene and protein expression between wild type and CPSF6 knock-down cells and their dependency on temperature. Analyzing differential responses upon temperature changes in wild type and CPSF6 knockdown cells reveals candidate genes underlying circadian temperature compensation. We identify that eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) is among these candidates. EIF2S1 is known as a master regulator of cellular stress responses that additionally regulates circadian rhythms. We show that knockdown of EIF2S1 furthermore impairs temperature compensation, suggesting that the role of CPSF6 in temperature compensation may be mediated by its regulation of EIF2S1.

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“…This gene has been implicated in multiple sclerosis, which is an inflammatory disease of the central nervous system 16 . Additionally, FIP1L1 is associated with pre-mRNA 3'end formation and has been implicated in immunological function by cooperating with IL-5 17,18 .…”

Section: Discussionmentioning

confidence: 99%

Increased expression of genetically-regulatedFLT3implicated in Tourette’s Syndrome

Liao

Vuokila

Catoire

et al. 2019

Preprint

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Tourette's Syndrome (TS) is a neurodevelopmental disorder that is characterized by motor and phonic tics. A recent TS genome-wide association study (GWAS) identified a genome-wide significant locus. However, determining the biological mechanism of GWAS signals remains difficult. Here, we conduct a TS transcriptome-wide association study (TWAS) consisting of 4,819 cases and 9,488 controls and found that increased expression of FLT3 in the dorsolateral prefrontal cortex (DLPFC) is associated with TS. We further showed that there is global dysregulation of FLT3 across several brain regions and probabilistic causal fine-mapping of the TWAS signal prioritizes FLT3 with a posterior inclusion probability of 0.849. We validated the gene's expression in 100 lymphoblastoid cell lines, establishing that TS cells had a 1.72 increased fold change compared to controls. A phenome-wide association study points towards FLT3 having links with immune-related pathways such as monocyte count. We also identify several splicing events in MPHOSPH9, CSGALNACT2 and FIP1L1 associated with TS, which are also implicated in immune function. This analysis of expression and splicing begins to explore the biology of TS GWAS signals.

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Identification and Characterization of Transcripts Regulated by Circadian Alternative Polyadenylation in Mouse Liver

Cited by 21 publications

References 86 publications

The circadian clock shapes the Arabidopsis transcriptome by regulating alternative splicing and alternative polyadenylation

The circadian clock shapes the Arabidopsis transcriptome by regulating alternative splicing and alternative polyadenylation

An integrative omics approach reveals posttranscriptional mechanisms underlying circadian temperature compensation

Increased expression of genetically-regulatedFLT3implicated in Tourette’s Syndrome

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