A methyl transferase links the circadian clock to the regulation of alternative splicing
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE18808
PROVIDER: PRJNA121225 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Study on differential gene expression and splicing between wildtype and clock mutants. This study is part of a comparative analysis of the role of Protein Methyltransferase 5 in the regulation of transcriptional and post-transcriptional processes simultaneously in Arabidopsis and Drosophila. Circadian rhythms allow organisms to time biological processes to the most appropriate phases of the day/night cycle1. Post-transcriptional regulation is emerging as an important component of circadian networks2-6, but the molecular mechanisms linking the circadian clock to the control of RNA processing are largely unknown. Here we show that Protein Arginine Methyl Transferase 5 (PRMT5), which transfers methyl groups to arginine residues present in histones7 and Sm spliceosomal proteins8,9, links the circadian clock to the control of alternative splicing in plants. Mutations in prmt5impair multiple circadian rhythms in Arabidopsis thaliana and this phenotype is caused, at least in part, by a strong alteration in alternative splicing of the core-clock gene PSEUDO RESPONSE REGULATOR 9 (PRR9). Furthermore, genome wide studies show that PRMT5 contributes to regulate many pre-mRNA splicing events most likely modulating 5´splice site (5´ss) recognition. PRMT5 expression shows daily and circadian oscillations, and this contributes to mediate the circadian regulation of expression and alternative splicing of a subset of genes. Circadian rhythms in locomotor activity are also disrupted in dart5, a mutant affected in the Drosophila melanogaster PRMT5 homolog, and this is associated with alterations in splicing of the core-clock gene period (per) and several clock associated genes. Our results reveal a key role for PRMT5 in the regulation of alternative splicing and indicate that the interplay between the circadian clock and the regulation of alternative splicing by PRMT5 constitutes a common mechanism that helps organisms to synchronize physiological processes with daily changes in environmental conditions.
2010-08-24 | GSE18808 | GEO
Project description:One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ul RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at â80 degrees C until use. Keywords: SuperSeries This reference Series links data in the following related Series: GSE3746 Circadian skeletal muscle_wt and Clock mutants GSE3748 Circadian liver_wt and Clock mutants
2010-06-12 | E-GEOD-3751 | biostudies-arrayexpress
Project description:Circadian clock dysfunction in human omental fat links obesity to metabolic inflammation
| PRJNA627226 | ENA
Project description:Purpose: Circadian clock in plants temporally coordinates biological processes throughout the day synchronizing gene expression with environmental changes. Here, we examined the genome-wide circadian and diurnal control of Arabidopsis transcriptome using high throughout RNA-seq approach. Methods: Transcriptional and posttranscritional profiles were identified and characterized for Arabidopsis seedlings grown under continuous light or long-day condition (16 h light/8 h dark) for one day (each condition has two biological replicates). Results: We show that rhythmic posttranscriptional regulation is also a significant factor for genome-wide profile of circadian plant transcriptome. Two major posttranscriptioal mechanisms alternative splicing (AS) and alternative polyadenylation (APA) show circadian rhythmicity, resulting from the oscillation in the genes invovled in AS and APA. Conclusions: Arabidopsis circadian clock not only controls the transcription of genes, but also affects their posttranscriptional regulation through regulating AS and APA.
2020-01-14 | GSE137732 | GEO
Project description:The non-canonical initiation factor DENR promotes translation reinitiation on uORF-containing mRNAs. Moreover, DENR depletion shortens circadian period in mouse fibroblasts, suggesting that uORF usage and reinitiation regulate clock function. To identify DENR-regulated translation events transcriptome-wide and, in particular, specific core clock transcripts affected by this mechanism, we have used ribosome profiling in DENR-deficient NIH3T3 cells. We found 240 transcripts with altered translation rate, and used linear regression analysis to extract uORF features predictive of DENR dependance. Among core clock genes, we identified Clock as a DENR target. Using Clock 5'UTR mutants, we mapped the specific uORF through which DENR acts to regulate CLOCK protein biosynthesis. Notably, these experiments identified an alternative downstream start codon, which likely represents the true CLOCK N-terminus. Our findings provide insights into uORF-mediated translational regulation that can regulate the mammalian circadian clock and gene expression at large.
2019-04-01 | GSE116221 | GEO
Project description:The non-canonical initiation factor DENR promotes translation reinitiation on uORF-containing mRNAs. Moreover, DENR depletion shortens circadian period in mouse fibroblasts, suggesting that uORF usage and reinitiation regulate clock function. To identify DENR-regulated translation events transcriptome-wide and, in particular, specific core clock transcripts affected by this mechanism, we have used ribosome profiling in DENR-deficient NIH3T3 cells. We found 240 transcripts with altered translation rate, and used linear regression analysis to extract uORF features predictive of DENR dependance. Among core clock genes, we identified Clock as a DENR target. Using Clock 5'UTR mutants, we mapped the specific uORF through which DENR acts to regulate CLOCK protein biosynthesis. Notably, these experiments identified an alternative downstream start codon, which likely represents the true CLOCK N-terminus. Our findings provide insights into uORF-mediated translational regulation that can regulate the mammalian circadian clock and gene expression at large.
2019-04-01 | GSE124790 | GEO
Project description:The circadian clock is comprised of proteins that form negative feedback loops, which regulate the timing of global gene expression in a coordinated 24 hour cycle. As a result, the plant circadian clock is responsible for regulating numerous physiological processes central to growth and survival. To date, most plant circadian clock studies have relied on diurnal transcriptome changes to elucidate molecular connections between the circadian clock and observable phenotypes in wild-type plants. Here, we have combined high-throughput RNA-sequencing and mass spectrometry to comparatively characterize the lhycca1, prr7prr9, gi and toc1 circadian clock mutant rosette transcriptome and proteome at the end-of-day and end-of-night.
2018-01-02 | PXD004763 | Pride
Project description:One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ?l RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at â80?C until use. Keywords: time course duplicates consisted of pools from independent mice
2010-06-11 | E-GEOD-3748 | biostudies-arrayexpress
Project description:Circadian clocks generate endogenous rhythms in most organisms from cyanobacteria to humans and facilitate entrainment to environmental diurnal cycles, thus conferring a fitness advantage. Both transcriptional and posttranslational mechanisms are prominent in the basic network architecture of circadian systems. Posttranscriptional regulation, including mRNA processing, is emerging as a critical step for the clock function. However, little is known about the molecular mechanisms linking RNA metabolism to the circadian clock network. Here we report that a conserved SNW/SKIP domain protein, SKIP, a splicing factor and component of the spliceosome, is involved in the posttranscriptional regulation of circadian clock genes in Arabidopsis. Mutation in SKIP lengthens the circadian period in a temperature sensitive manner, affects light input and the sensitivity of light resetting to the clock. SKIP physically interacts with the spliceosomal splicing factor SR45 and associates with the pre-mRNA of clock genes, such as PRR7 and PRR9, and is necessary for the regulation of their alternative splicing and mRNA maturation. Genome-wide investigations reveal that SKIP functions in regulating alternative splicing of many genes, presumably through modulating recognition or cleavage of 5' and 3' splicing site. Our study addresses a fundamental question on how the mRNA splicing machinery contributes to circadian clock functions at a posttranscriptional level. Our findings revealed that AtSKIP is a splicing factor and a component of spliceosome. To further investigate effects of mutation in SKIP on the genome-wide changes of alternative splicing, we performed ultra-highthroughput RNA sequencing, using 10-day old seedlings. Two biological replicates for both wild type (Col-0) and skip-2 were designed.
2012-12-13 | E-GEOD-32216 | biostudies-arrayexpress
Project description:Influence of diet and neuronal clk (clock) activity on hemolymph proteomics. We have shown that as photoreceptors die (in the fly) they necrose, which results in their intercellular contents leaking into the hemolymph. We hypothesize that this process is regulated by diet and circadian clock control.
Analysis of differential protein expression in the hemolymph from flies reared on a high protein diet. Comparison of flies with and without a functional circadian clock within their photoreceptors.
Species/Strain: Drosophila, Elav-GeneSwitch-GAL4>UAS-Clk-DN1 (+/- RU486), female
2021-01-30 | MSV000086781 | MassIVE