Extensive allele-specific translational regulation
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD002337
REPOSITORIES: ENA
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Project description: Not available
| S-EPMC4562498 | biostudies-literature
Project description:Extensive Transcriptional and Translational Regulation Occur During the Maturation of Malaria Parasite Sporozoites
| PRJNA453153 | ENA
Project description:Though sequence differences between alleles are often limited to a few polymorphisms, these differences can cause large and widespread allelic variation at the expression level. Such allele-specific expression (ASE) has been extensively explored at the level of transcription but not translation. Here we measured ASE in the diploid yeast Candida albicans at both the transcriptional and translational levels using RNA-seq and ribosome profiling, respectively. Since C. albicans is an obligate diploid, our analysis isolates ASE arising from cis elements in a natural, non-hybrid organism, where allelic effects reflect evolutionary forces. Importantly, we find that ASE arising from translation is of a similar magnitude as transcriptional ASE, both in terms of the number of genes affected and the magnitude of the bias. We further observe coordination between ASE at the levels of transcription and translation for single genes. Specifically, reinforcing relationships—where transcription and translation favor the same allele—are more frequent than expected by chance, consistent with selective pressure tuning ASE at multiple regulatory steps. Finally, we parameterize alleles based on a range of properties and find that SNP location and predicted mRNA-structure stability are associated with translational ASE in cis. Since this analysis probes more than 4,000 allelic pairs spanning a broad range of variations, our data provide a genome-wide view into the relative impacts of cis elements that regulate translation.
2014-03-14 | GSE52236 | GEO
Project description:Though sequence differences between alleles are often limited to a few polymorphisms, these differences can cause large and widespread allelic variation at the expression level. Such allele-specific expression (ASE) has been extensively explored at the level of transcription but not translation. Here we measured ASE in the diploid yeast Candida albicans at both the transcriptional and translational levels using RNA-seq and ribosome profiling, respectively. Since C. albicans is an obligate diploid, our analysis isolates ASE arising from cis elements in a natural, non-hybrid organism, where allelic effects reflect evolutionary forces. Importantly, we find that ASE arising from translation is of a similar magnitude as transcriptional ASE, both in terms of the number of genes affected and the magnitude of the bias. We further observe coordination between ASE at the levels of transcription and translation for single genes. Specifically, reinforcing relationshipsM-bM-^@M-^Twhere transcription and translation favor the same alleleM-bM-^@M-^Tare more frequent than expected by chance, consistent with selective pressure tuning ASE at multiple regulatory steps. Finally, we parameterize alleles based on a range of properties and find that SNP location and predicted mRNA-structure stability are associated with translational ASE in cis. Since this analysis probes more than 4,000 allelic pairs spanning a broad range of variations, our data provide a genome-wide view into the relative impacts of cis elements that regulate translation. Two biological replicates of WT Candida albicans ribosome profiling and RNA-seq
2014-03-14 | E-GEOD-52236 | biostudies-arrayexpress
Project description:Eukaryotic cells are constantly challenged by the presence of reactive oxygen species, which play an important role in aging and human disease progression. In particular, acute oxidative stress can lead to extensive damage to cellular DNA, proteins, and lipids and can trigger a response that remodels the transcriptional and translational state of the cell. Although a number of previous studies have profiled the relative changes in mRNA and protein and more studies revealing the dynamics of transcription and translation in response to stress are starting to emerge, a quantitative view of this response has been lacking. Here, we have applied quantitative methods to characterize the time dynamics of mRNA and protein levels in the oxidative stress response of the fission yeast Schizosaccharomyces pombe, which has allowed us to perform dynamic modeling of responsive genes in units of copies per cell. Analysis of the resulting time dynamics provided a new genome-wide view of the scale, timing and rates of transcription and translation in the transient response. The majority of dynamic genes were observed to be responsive in their mRNA or protein levels alone implying extensive translational regulation. Nevertheless, modeling of genes with responsive mRNA and protein levels showed that protein levels could, in a majority of these cases, be accurately predicted with constant translation and decay rates while a minority benefited from explicit translation delay parameters. A number of independent features, e.g. measures of codon bias, ribosome occupancy, etc., were found to be less correlated to maximally perturbed protein levels than steady-state levels. Codon bias measures were more correlated than mRNA levels to quantitative protein levels at both perturbed and un-perturbed states. Measures of translation activity, on the other hand, were only significantly correlated at steady state. In total 32 samples: 11 for stressed time series R1, 11 for stressed time series R2, 5 for control time series C1 and 5 for control time series C2
2015-03-01 | E-GEOD-62120 | biostudies-arrayexpress
Project description:Selective maintenance of genomic methylation imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions (ICRs) in early mouse embryos and ES cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. In addition, several cases of human transient neonatal diabetes (TND) are associated with somatic mutations in ZFP57 coding sequence. Here we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice assigning allele specificity to approximately two thirds of all binding sites. While half of these are biallelic and include ERV targets, the rest show mono-allelic binding based either on parental-origin or on genetic background of the allele. Parental-origin allele-specific binding was methylation-dependent and mapped only to imprinted DMRs established in the germline (gDMRs). No binding was evident at secondary somatically-derived DMRs. ZFP57-bound gDMRs can predict imprinted gene expression and we identify new imprinted genes, including the Fkbp6 gene with a critical function in mouse male germ cell development. Genetic-background specific sequence differences also influence ZFP57 binding. We show that genetic variation that disrupts the consensus binding motif and its methylation is associated with mono-allelic expression of neighbouring genes. The work described here uncovers further roles for ZFP57 mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined mono-allelic gene expression. Input and Zfp57 CHiP-Seq profiles of hybrid Black6/Cast ES cells were generated by sequencing using the Illumina GAIIx platform.
2015-05-08 | E-GEOD-55382 | biostudies-arrayexpress
Project description:We analysed the translatome and transcriptome of Arabidopsis thaliana Col-0 WT at five distinct physiological states during seed germination. The aim was to obtain a global overview of genes under translational control during seed-seedling transition.
2016-11-18 | GSE65780 | GEO
Project description:Eukaryotic cells are constantly challenged by the presence of reactive oxygen species, which play an important role in aging and human disease progression. In particular, acute oxidative stress can lead to extensive damage to cellular DNA, proteins, and lipids and can trigger a response that remodels the transcriptional and translational state of the cell. Although a number of previous studies have profiled the relative changes in mRNA and protein and more studies revealing the dynamics of transcription and translation in response to stress are starting to emerge, a quantitative view of this response has been lacking. Here, we have applied quantitative methods to characterize the time dynamics of mRNA and protein levels in the oxidative stress response of the fission yeast Schizosaccharomyces pombe, which has allowed us to perform dynamic modeling of responsive genes in units of copies per cell. Analysis of the resulting time dynamics provided a new genome-wide view of the scale, timing and rates of transcription and translation in the transient response. The majority of dynamic genes were observed to be responsive in their mRNA or protein levels alone implying extensive translational regulation. Nevertheless, modeling of genes with responsive mRNA and protein levels showed that protein levels could, in a majority of these cases, be accurately predicted with constant translation and decay rates while a minority benefited from explicit translation delay parameters. A number of independent features, e.g. measures of codon bias, ribosome occupancy, etc., were found to be less correlated to maximally perturbed protein levels than steady-state levels. Codon bias measures were more correlated than mRNA levels to quantitative protein levels at both perturbed and un-perturbed states. Measures of translation activity, on the other hand, were only significantly correlated at steady state.
2015-03-01 | GSE62120 | GEO
Project description:Translational regulation of acetogenesis in Acetobacterium woodii
| PRJEB33460 | ENA
Project description:Selective maintenance of genomic methylation imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions (ICRs) in early mouse embryos and ES cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. In addition, several cases of human transient neonatal diabetes (TND) are associated with somatic mutations in ZFP57 coding sequence. Here we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice assigning allele specificity to approximately two thirds of all binding sites. While half of these are biallelic and include ERV targets, the rest show mono-allelic binding based either on parental-origin or on genetic background of the allele. Parental-origin allele-specific binding was methylation-dependent and mapped only to imprinted DMRs established in the germline (gDMRs). No binding was evident at secondary somatically-derived DMRs. ZFP57-bound gDMRs can predict imprinted gene expression and we identify new imprinted genes, including the Fkbp6 gene with a critical function in mouse male germ cell development. Genetic-background specific sequence differences also influence ZFP57 binding. We show that genetic variation that disrupts the consensus binding motif and its methylation is associated with mono-allelic expression of neighbouring genes. The work described here uncovers further roles for ZFP57 mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined mono-allelic gene expression.
2015-05-08 | GSE55382 | GEO