Passive shaping of intra- and intercellular m6A dynamics via mRNA metabolism
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PROVIDER: PRJNA1137857 | ENA |
REPOSITORIES: ENA
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Project description: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.
2024-07-25 | GSE272629 | GEO
Project description:N6-methyladenosine (m6A) is the most abundant mRNA modification, primarily implicated in controlling mRNA stability. The distribution of m6A varies considerably between and within species, and genetic variants associated with differences in m6A levels between humans have been associated with disease. Yet, the determinants governing m6A variability are poorly understood: It is unclear whether it is driven by changes in genetic sequences (‘cis’) or cellular environments (‘trans’) and what its underlying mechanisms are. Here we dissect these determinants via interspecies hybrids in yeast and mammalian systems, allowing us to interrogate methylation at two distinguishable alleles in a shared environment. We find that m6A evolution is driven primarily in ‘cis’, and identify two mechanisms driving m6A changes: (1) Sequence variations leading to formation/disruption of m6A consensus motifs, and (2) Changes in local mRNA secondary structure, whereby RNA structuredness inhibits m6A formation. We demonstrate that secondary structure is causal, and that gain and loss of structure - even when driven by mutations distant from the modified position - are sufficient to abolish and acquire methylation, respectively. Using intra-species hybrids, massively parallel reporter assays and reanalyzing m6A-QTLs among 60 human individuals, we reveal the combined role of sequence and structure in shaping variability in m6A levels also across individuals from the same species. Finally, we demonstrate that differences in m6A levels between homologous genes lead to allele-specific changes in gene expression. Our findings thus define the determinants governing m6A evolution and diversity and characterize the consequences thereof on gene expression regulation.
2024-01-24 | GSE232450 | GEO
Project description:Cyanobacterial sigma factor controls biofilm-promoting genes through intra- and intercellular pathways
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Project description:Gene expression in the rat dentate gyrus following passive avoidance training. Keywords: time-course
2004-12-01 | GSE1095 | GEO
Project description:N6-methyladenosine (m6A) is a widespread reversible chemical modification of RNAs, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m6A modified (âm6A levelsâ), or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad range of non-stoichiometric m6A levels with cell type specificity. At the level of isoform characterization, we discovered widespread differences in use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3â untranslated regions (3â-UTRs), while nonmethylated transcript isoforms tend to use distal APA sites. m6A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m6A modifications. m6A-LAIC-seq of H1-ESC and GM12878 cell lines, each cell line has two replicates
2016-06-24 | E-GEOD-66086 | biostudies-arrayexpress
Project description:N6-methyladenosine (m6A) is one of the most abundant modifications in eukaryotic RNA. Recent mapping of m6A methylomes in mammals, yeast, and plants as well as characterization of m6A methyltransferases, demethylases, and binding proteins have revealed regulatory functions of this dynamic RNA modification. In bacteria, although m6A is present in ribosomal RNA (rRNA), its occurrence in messenger RNA (mRNA) still remains elusive. Here, we used liquid chromatography-mass spectrometry (LC-MS) to calculate the m6A/A ratio in mRNA from a wide range of bacterial species, which demonstrates that m6A is an abundant mRNA modification in tested bacteria. Subsequent transcriptome-wide m6A profiling in Escherichia coli and Pseudomonas aeruginosa revealed a conserved distinct m6A pattern that is significantly different from that in eukaryotes. Most m6A peaks are located inside open reading frames (ORF), and carry a unique consensus motif (GCCAU). Functional enrichment analysis of bacterial m6A peaks indicates that the majority of m6A-modified transcripts are associated with respiration, amino acids metabolism, stress response, and small RNAs genes, suggesting potential regulatory roles of m6A in these pathways. m6A profiling in E.coli and P.aeruginosa mRNA
2015-07-08 | E-GEOD-65347 | biostudies-arrayexpress
Project description:m6A is a ubiquitous RNA modification in eukaryotes. Transcriptome-wide m6A patterns in Arabidopsis have been assayed recently. However, m6A differential patterns among organs have not been well characterized. The goal of the study is to comprehensively analyze m6A patterns of numerous types of RNAs, the relationship between transcript level and m6A methylation extent, and m6A differential patterns among organs in Arabidopsis. In total, 18 libraries were sequneced. For the 3 organs: leaf, flower and root, each organ has mRNA-Seq, m6A-Seq and Input sequenced. And each sequence has 2 replicats.
2015-10-28 | E-GEOD-72706 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE36958: Gene expression profiles of WT and ime4-/- mutant yeast cells, under vegetative and meiosis-inducing conditions GSE37001: METTL3 KD in HepG2 cells GSE37002: m6A mapping in human RNA (with treatments) GSE37003: m6A mapping in human RNA (untreated) GSE37004: m6A mapping in mouse RNA (mouse liver and human brain) Refer to individual Series
2012-04-24 | E-GEOD-37005 | biostudies-arrayexpress
Project description:We developed a novel approach, m6A-seq, for high-resolution mapping of the transcriptome-wide m6A landscape, based on antibody-mediated capture followed by massively parallel sequencing. Identification of m6A modified sequences in HepG2 cells.
2012-04-25 | E-GEOD-37003 | biostudies-arrayexpress
Project description:Cyanobacteria frequently constitute integral components of microbial communities known as phototrophic biofilms, which are widespread in various environments and hold significant industrial relevance. Previous studies of the model cyanobacterium Synechococcus elongatus PCC 7942 revealed that its planktonic growth habit results from a biofilm-suppression mechanism that depends on an extracellular inhibitor, an observation that opens the door to investigating cyanobacterial intercellular communication. Here, we demonstrate that the RNA polymerase sigma factor SigF1, is required for this biofilm-suppression mechanism and suggest that sigF1-inactivation impairs secretion of the biofilm inhibitor. The S. elongatus paralog SigF2, however, is not involved in biofilm regulation. Comprehensive transcriptome analyses identified distinct regulons under the control of each of these sigma factors. Additional data indicate that SigF1 regulates biofilm through its involvement in transcriptional induction of genes that include those for the primary pilus subunit: sigF1 inactivation both prevents pilus assembly and abrogates secretion of the biofilm inhibitor. Consequently, expression is significantly upregulated for the ebfG-operon that encodes matrix components and the genes that encode the corresponding secretion system. Thus, this study uncovers a basic regulatory component of cyanobacterial intercellular communication, a field that is in its infancy. Elevated expression of biofilm-promoting genes in a sigF1 mutant supports an additional layer of regulation by SigF1 that operates via an intracellular mechanism.
2024-09-13 | GSE254350 | GEO