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Series GSE272629 Query DataSets for GSE272629
Status Public on Jul 25, 2024
Title Passive shaping of intra- and intercellular m6A dynamics via mRNA metabolism
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Other
Summary m6A is the most widespread mRNA modification and is primarily implicated in controlling mRNA stability. Fundamental questions pertaining to m6A are the extent to which it is dynamically modulated within cells and across stimuli, and the forces underlying such modulation. Prior work has focused on investigating active mechanisms governing m6A levels, such as recruitment of m6A writers or erasers leading to either ‘global’ or ‘site-specific’ modulation. Here, we propose that changes in m6A levels across subcellular compartments and biological trajectories may result from passive changes in gene-level mRNA metabolism. To predict the intricate interdependencies between m6A levels, mRNA localization, and mRNA decay, we establish a differential model ‘m6ADyn’ encompassing mRNA transcription, methylation, export, and m6A-dependent and independent degradation. We validate the predictions of m6ADyn in the context of intracellular m6A dynamics, where m6ADyn predicts associations between relative mRNA localization and m6A levels, which we experimentally confirm. We further explore m6ADyn predictions pertaining to changes in m6A levels upon controlled perturbations of mRNA metabolism, which we also experimentally confirm. Finally, we demonstrate the relevance of m6ADyn in the context of cellular heat stress response, where genes subjected to altered mRNA product and export also display predictable changes in m6A levels, consistent with m6ADyn predictions. Our findings establish a framework for dissecting m6A dynamics and suggest the role of passive dynamics in shaping m6A levels in mammalian systems.
 
Overall design These sereies comprises different experimental series with varying treatments. There is: WT and Mettl3 KO cytoplasmic and nucelar fraction followed by RNA-seq. Cytoplasmic and nucelar fractionation experiment of NIH3T3 cells followed by m6A-seq2. Cytoplasmic and nucelar fraction of pMEFs cells followed by m6A-seq2. CPT treatement followed by m6A-seq2 in MCF7 cells. Actinomycin D timecourse followed by m6A-seq2 in A9 cells. YTHDF1-3 triple knock-down experiment via siRNA followed by m6A-seq2 in NIH3T3 cells. YTHDF1-3 triple knock-down experiment via siRNA followed cytoplasmic and nucelar fraction followed by RNA-seq in NIH3T3 cells. Heat stress timecourse followed by m6A-seq2 in WT primary MEFs. Heat stress timecourse followed by m6A-seq2 in HSF1 KO primary MEFs. Cytoplasmic and nucelar fractionation experiment followed by RNA-seq after heat stress in WT primary MEFs. Cytoplasmic and nucelar fractionation experiment followed by RNA-seq after heat stress in HSF1 KO primary MEFs.
 
Contributor(s) Dierks D, Schwartz S, Shachar R, Nir R, Garcia-Campos MA, Uzonyi A, Toth U, Rossmanith W, Lasman L, Slobodin B, Hanna JH, Antebi Y, Scherz-Shouval R, Wiener D
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Submission date Jul 19, 2024
Last update date Jan 15, 2025
Contact name David Dierks
E-mail(s) david.dierks@weizmann.ac.il
Organization name Weizmann Institute of Science
Department Molecular Genetics
Lab Schraga Schwartz
Street address Herzl St 234, Weizmann Institute of Science to the Department of Biomolecular Sciences, Laboratory of Dr. Scherz-Shouval
City Rehovot
State/province Central District
ZIP/Postal code 7610001
Country Israel
 
Platforms (3)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (128)
GSM8407940 cytosol, mESC WT
GSM8407941 cytosol, mESC Mettl3 KO
GSM8407942 nuclear, mESC WT
Relations
BioProject PRJNA1137857

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Supplementary file Size Download File type/resource
GSE272629_RAW.tar 69.4 Mb (http)(custom) TAR (of RESULTS, TXT)
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Raw data are available in SRA

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