Translation variation across genetic backgrounds reveals a post-transcriptional buffering signature in yeast
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ABSTRACT:
PROVIDER: PRJNA726548 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26680410.fastq.gz | Fastqsanger.gz | |||
| SRR26680411.fastq.gz | Fastqsanger.gz | |||
| SRR26680412.fastq.gz | Fastqsanger.gz | |||
| SRR26680413.fastq.gz | Fastqsanger.gz | |||
| SRR26680414.fastq.gz | Fastqsanger.gz |
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Project description:Gene expression is known to vary among individuals, and this variability can impact the phenotypic diversity observed in natural populations. While the transcriptome and proteome have been extensively studied, little is known about the translation process itself. Here, we therefore performed ribosome and transcriptomic profiling on a genetically and ecologically diverse subset of natural isolates of the Saccharomyces cerevisiae yeast. Interestingly, we found that the Euclidean distances between each profile and the expression fold changes in each pairwise isolate comparison were approximately 10% higher at the transcriptomic level. This observation clearly indicates that the transcriptional variation observed in the different isolates is buffered through a phenomenon known as post-transcriptional buffering at the translation level. Furthermore, this phenomenon seemed to have a specific signature by preferentially affecting essential genes as well as genes involved in complex-forming proteins, and low transcribed genes. We also explored the translation of the S. cerevisiae pangenome and found that the accessory genes related to introgression events displayed similar transcription and translation levels as the core genome. By contrast, genes acquired through horizontal gene transfer events tended to be less efficiently translated. Together, our results highlight both the extant and signature of the post- transcriptional buffering.
2024-02-01 | GSE173654 | GEO
Project description:Gene expression is known to vary among individuals, and this variability can impact the phenotypic diversity observed in natural populations. While the transcriptome and proteome have been extensively studied, little is known about the translation process itself. Here, we therefore performed ribosome and transcriptomic profiling on a genetically and ecologically diverse set of natural isolates of the Saccharomyces cerevisiae yeast. Interestingly, we found that the Euclidean distances between each profile and the expression fold changes in each pairwise isolate comparison were higher at the transcriptomic level. This observation clearly indicates that the transcriptional variation observed in the different isolates is buffered through a phenomenon known as post-transcriptional buffering at the translation level. Furthermore, this phenomenon seemed to have a specific signature by preferentially affecting essential genes as well as genes involved in complex-forming proteins, and low transcribed genes. We also explored the translation of the S. cerevisiae pangenome and found that the accessory genes related to introgression events displayed similar transcription and translation levels as the core genome. By contrast, genes acquired through horizontal gene transfer events tended to be less efficiently translated. Together, our results highlight both the extent and signature of the post-transcriptional buffering.
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Project description:Differences in gene regulation between human and closely related species influence phenotypes that are distinctly human. While gene regulation is a multi-step process, the majority of research concerning divergence in gene regulation among primates has focused on transcription. To gain a comprehensive view of gene regulation, we surveyed genome-wide ribosome occupancy, which reflects levels of protein translation, in lymphoblastoid cell lines derived from human, chimpanzee and rhesus macaque. We further integrated mRNA and protein level measurements collected from matching cell lines. We find that, in addition to transcriptional regulation, the major factor determining protein level divergence between human and closely related species is post-translational buffering. Inter-species divergence in transcription is generally propagated to the level of protein translation. In contrast, gene expression divergence is often attenuated post-translationally, potentially mediated through post-translational modifications. Results from our analysis indicate that post-translational buffering is a conserved mechanism that led to relaxation of selective constraint on transcript levels in humans.
2018-05-10 | GSE71808 | GEO
Project description:Gene expression is a dynamic process regulated on several layers starting with transcription, mRNA export, translation and finally, mRNA degradation. While subsequent layers heavily influence each other, it is not clear if the most extreme layers, chromatin architecture and mRNA decay are linked. Here, we show that changes in nascent transcription mediated by mutating H3K56 to alanine are buffered at a post-transcriptional level by the Pumilio protein Puf5, which stabilizes transcripts in a context-dependent manner. Depleting Puf5 in an H3K56A background leads to downregulation of its direct targets, largely consisting of ribosomal protein genes. This is followed by a decrease in translation efficiency and finally, cell cycle arrest. Importantly, we show that this phenomenon of post-transcriptional buffering is not only linked to H3K56A, but might be a more widespread phenomenon to ensure physiological mRNA levels and to maintain cellular homeostasis.
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Project description:Translational buffering refers to the regulation of ribosome occupancy to offset the effects of transcriptional variation. While previous work reported translational buffering in a limited set of conditions, it remains unknown whether this is an intrinsic property of specific genes across a large number of different cell types. To identify genes exhibiting this phenomenon on a global scale and across different experimental conditions, we uniformly analyzed 1515 matched ribosome profiling and RNA-seq datasets from human and mouse tissues or cell lines. This resource enabled us to determine the set of genes exhibiting translational buffering by comparative analysis of variation at ribosome occupancy and the RNA levels across cell types and the relationship between mRNA abundance and translation efficiency. We demonstrate that translational buffering is a conserved property of genes using homologous gene pairs from humans and mice. Genes exhibiting translational buffering have lower variation in protein abundance in cancer cell lines, primary human tissues and mouse samples. Moreover, we observed that translationally buffered genes are more likely to be haploinsufficient and triplosensitive suggesting a demand for stringent dosage limits in these genes. We hypothesized two models of translational buffering, namely “differential accessibility model” and “change in translation initiation rate model”. Our experiment suggests that some transcripts conform to the former and others align with the alternate model. Overall, our work broadens the catalog of genes subjected to translational buffering, underscores the characteristics of genes that demonstrate this phenomenon and additionally provides an insight into the rationale driving this effect.
2025-06-24 | GSE297442 | GEO
Project description:Gene expression is a dynamic process regulated on several layers starting with transcription, mRNA export, translation and finally, mRNA degradation. While subsequent layers heavily influence each other, it is not clear if the most extreme layers, chromatin architecture and mRNA decay are linked. Here, we show that changes in nascent transcription mediated by mutating H3K56 to alanine are buffered at a post-transcriptional level by the Pumilio protein Puf5, which stabilizes transcripts in a context-dependent manner. Depleting Puf5 in an H3K56A background leads to downregulation of its direct targets, largely consisting of ribosomal protein genes. This is followed by a decrease in translation efficiency and finally, cell cycle arrest. Importantly, we show that this phenomenon of post-transcriptional buffering is not only linked to H3K56A, but might be a more widespread phenomenon to ensure physiological mRNA levels and to maintain cellular homeostasis.
2021-07-19 | E-MTAB-10105 | biostudies-arrayexpress
Project description:RNA buffering upon transcriptional distorsion
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Project description:Transcriptional buffering compensates for eIF4E deficiency 2 in mRNA translation in transformed but not normal cells
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Project description:Protein expression is a major link in the genotype-phenotype relationship, and processes affecting protein abundances, such as rates of transcription and translation, could contribute to phenotypic evolution if they generate heritable variation. Recent work has suggested that mRNA abundances do not accurately predict final protein abundances, which would imply that post-transcriptional regulatory processes contribute significantly to phenotypes. Post-transcriptional processes also appear to buffer changes in transcriptional patterns as species diverge, suggesting that the transcriptional changes have little or no effect on the phenotypes under study. We tested for concordance between mRNA and protein expression levels in snake venoms by means of mRNA-seq and quantitative mass spectrometry for 11 snakes representing 10 species, six genera, and three families. In contrast to most previous work, we found high correlations between venom-gland transcriptomes and venom proteomes for ten of our 11 comparisons. We tested for protein-level buffering of transcriptional changes during species divergence by comparing the difference between transcript abundance and protein abundance for three pairs of species and one intraspecific pair. We found no evidence for buffering during divergence of our three species pairs but did find evidence for protein-level buffering for our single intraspecific comparison, suggesting that buffering, if present, was a transient phenomenon in venom divergence. Our results demonstrated that post-transcriptional mechanisms did not contribute significantly to phenotypic evolution in venoms and suggest a more prominent and direct role for cis-regulatory evolution in phenotypic variation, particularly for snake venoms.
2015-11-09 | PXD002837 | Pride
Project description:Post-transcriptional buffering of low nascent RNA transcription by Puf5
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