Functional and transcriptional profiling of non-coding RNAs in yeast reveal context-dependent phenotypes and in trans effects on the protein regulatory network

Non-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts. Novel functional ncRNAs, SUT125, SUT126, SUT035 and SUT532 that act in trans by modulating transcription factors were identified. Furthermore, we described the impact of SUTs and CUTs in modulating coding gene expression in response to different environmental conditions, regulating important biological process such as respiration (SUT125, SUT126, SUT035, SUT432), steroid biosynthesis (CUT494, SUT053, SUT468) or rRNA processing (SUT075 and snR30). Overall, these data capture and integrate the regulatory and phenotypic network of ncRNAs and protein-coding genes, providing genome-wide evidence of the impact of ncRNAs on cellular homeostasis.

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Functional and transcriptional profiling of non-coding RNAs in yeast reveal context-dependent phenotypes and widespread in trans effects on the protein regulatory network

10.1101/2020.04.07.029611 ◽

2020 ◽

Author(s):

Laura Natalia Balarezo-Cisneros ◽

Steven Parker ◽

Marcin G Fraczek ◽

Soukaina Timouma ◽

Ping Wang ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Environmental Conditions ◽

Mode Of Action ◽

Protein Coding ◽

Protein Coding Genes ◽

Genome Wide ◽

In Trans ◽

Non Coding Rnas ◽

The Impact

AbstractNon-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts. Novel functional ncRNAs, SUT125, SUT126, SUT035 and SUT532 that act in trans by modulating transcription factors were identified. Furthermore, we described the impact of SUTs and CUTs in modulating coding gene expression in response of different environmental conditions, regulating important biological process such as respiration (SUT125, SUT126, SUT035, SUT432), steroid biosynthesis (CUT494, SUT530, SUT468) or rRNA processing (SUT075 and snR30). Overall, this data captures and integrates the regulatory and phenotypic network of ncRNAs and protein coding genes, providing genome-wide evidence of the impact of ncRNAs on cellular homeostasis.Author SummaryThe yeast genome contains 25% of non-coding RNA molecules (ncRNAs), which do not translate into proteins but are involved in regulation of gene expression. ncRNAs can affect nearby genes by physically interfering with their transcription (cis mode of action), or they interact with DNA, proteins or others RNAs to regulate the expression of distant genes (trans mode of action). Examples of cis-acting ncRNAs have been broadly described, however genome-wide studies to identify functional trans-acting ncRNAs involved in global gene regulation are still lacking. Here, we used the ncRNA yeast deletion collection to score their impact on cellular function in different environmental conditions. A group of 20 ncRNAs mutants with broad fitness diversity were selected to investigate their effect on the protein and ncRNA expression network. We showed a high correlation between altered phenotypes and global transcriptional changes, in an environmental dependent manner. We confirmed the widespread trans acting expressional regulation of ncRNAs in the genome and their role in affecting transcription factors. These findings support the notion of the involvement on ncRNAs in fine tuning the cellular expression via regulations of TFs, as an advantageous RNA-mediated mechanism that can be fast and cost-effective for the cells.

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Contribution of Retrotransposition to Developmental Disorders

10.1101/471375 ◽

2018 ◽

Cited By ~ 2

Author(s):

Eugene J. Gardner ◽

Elena Prigmore ◽

Giuseppe Gallone ◽

Petr Danecek ◽

Kaitlin E. Samocha ◽

...

Keyword(s):

Developmental Disorders ◽

De Novo ◽

Purifying Selection ◽

Mobile Genetic Elements ◽

Protein Coding ◽

Protein Coding Genes ◽

Genome Wide ◽

The Impact ◽

Transcribed Sequences

AbstractMobile genetic Elements (MEs) are segments of DNA which, through an RNA intermediate, can generate new copies of themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. As such, we have identified RT-derived events in 9,738 exome sequenced trios with DD-affected probands as part of the Deciphering Developmental Disorders (DDD) study. We have ascertained 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04% of probands), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we have estimated genome-wide germline ME mutagenesis and constraint and demonstrated that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.

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DUPLICATED RNA GENES IN TELEOST FISH GENOMES

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720008003886 ◽

2008 ◽

Vol 06 (06) ◽

pp. 1157-1175 ◽

Cited By ~ 8

Author(s):

DOMINIC ROSE ◽

JULIAN JÖRIS ◽

JÖRG HACKERMÜLLER ◽

KRISTIN REICHE ◽

QIANG LI ◽

...

Keyword(s):

Teleost Fish ◽

Copy Number ◽

Large Scale ◽

Genome Duplication ◽

Gene Duplications ◽

Teleost Fishes ◽

Protein Coding ◽

Protein Coding Genes ◽

Non Coding Rnas ◽

Rna Genes

Teleost fishes share a duplication of their entire genomes. We report here on a computational survey of structured non-coding RNAs (ncRNAs) in teleost genomes, focusing on the fate of fish-specific duplicates. As in other metazoan groups, we find evidence of a large number (11,543) of structured RNAs, most of which (~86%) are clade-specific or evolve so fast that their tetrapod homologs cannot be detected. In surprising contrast to protein-coding genes, the fish-specific genome duplication did not lead to a large number of paralogous ncRNAs: only 188 candidates, mostly microRNAs, appear in a larger copy number in teleosts than in tetrapods, suggesting that large-scale gene duplications do not play a major role in the expansion of the vertebrate ncRNA inventory.

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A description of large-scale metabolomics studies: increasing value by combining metabolomics with genome-wide SNP genotyping and transcriptional profiling

Journal of Endocrinology ◽

10.1530/joe-12-0144 ◽

2012 ◽

Vol 215 (1) ◽

pp. 17-28 ◽

Cited By ~ 18

Author(s):

Georg Homuth ◽

Alexander Teumer ◽

Uwe Völker ◽

Matthias Nauck

Keyword(s):

Blood Cells ◽

Large Scale ◽

Genetic Factors ◽

Association Studies ◽

Transcriptional Profiling ◽

Genome Wide Association Studies ◽

Protein Levels ◽

Future Developments ◽

Genome Wide ◽

Metabolome Data

The metabolome, defined as the reflection of metabolic dynamics derived from parameters measured primarily in easily accessible body fluids such as serum, plasma, and urine, can be considered as the omics data pool that is closest to the phenotype because it integrates genetic influences as well as nongenetic factors. Metabolic traits can be related to genetic polymorphisms in genome-wide association studies, enabling the identification of underlying genetic factors, as well as to specific phenotypes, resulting in the identification of metabolome signatures primarily caused by nongenetic factors. Similarly, correlation of metabolome data with transcriptional or/and proteome profiles of blood cells also produces valuable data, by revealing associations between metabolic changes and mRNA and protein levels. In the last years, the progress in correlating genetic variation and metabolome profiles was most impressive. This review will therefore try to summarize the most important of these studies and give an outlook on future developments.

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Coordinate regulation of long non-coding RNAs and protein-coding genes in germ-free mice

BMC Genomics ◽

10.1186/s12864-018-5235-3 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 15

Author(s):

Joseph Dempsey ◽

Angela Zhang ◽

Julia Yue Cui

Keyword(s):

Protein Coding ◽

Coordinate Regulation ◽

Germ Free ◽

Protein Coding Genes ◽

Non Coding Rnas

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The theory on and software simulating large-scale genomic data for genotype-by-environment interactions

BMC Genomics ◽

10.1186/s12864-021-08191-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Xiujin Li ◽

Hailiang Song ◽

Zhe Zhang ◽

Yunmao Huang ◽

Qin Zhang ◽

...

Keyword(s):

Large Scale ◽

Simulated Data ◽

Genomic Data ◽

Efficient Tool ◽

Phenotypic Data ◽

Genotype By Environment Interactions ◽

Genotype By Environment ◽

Threshold Trait ◽

Genome Wide ◽

Increasing Demand

Abstract Background With the emphasis on analysing genotype-by-environment interactions within the framework of genomic selection and genome-wide association analysis, there is an increasing demand for reliable tools that can be used to simulate large-scale genomic data in order to assess related approaches. Results We proposed a theory to simulate large-scale genomic data on genotype-by-environment interactions and added this new function to our developed tool GPOPSIM. Additionally, a simulated threshold trait with large-scale genomic data was also added. The validation of the simulated data indicated that GPOSPIM2.0 is an efficient tool for mimicking the phenotypic data of quantitative traits, threshold traits, and genetically correlated traits with large-scale genomic data while taking genotype-by-environment interactions into account. Conclusions This tool is useful for assessing genotype-by-environment interactions and threshold traits methods.

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PaperBLAST: Text-mining papers for information about homologs

10.1101/133041 ◽

2017 ◽

Author(s):

Morgan N. Price ◽

Adam P. Arkin

Keyword(s):

Text Mining ◽

Genome Sequencing ◽

Full Text ◽

Large Scale ◽

Scientific Literature ◽

Protein Sequences ◽

Protein Coding ◽

Link Protein ◽

Protein Coding Genes ◽

Link Type

AbstractLarge-scale genome sequencing has identified millions of protein-coding genes whose function is unknown. Many of these proteins are similar to characterized proteins from other organisms, but much of this information is missing from annotation databases and is hidden in the scientific literature. To make this information accessible, PaperBLAST uses EuropePMC to search the full text of scientific articles for references to genes. PaperBLAST also takes advantage of curated resources that link protein sequences to scientific articles (Swiss-Prot, GeneRIF, and EcoCyc). PaperBLAST’s database includes over 700,000 scientific articles that mention over 400,000 different proteins. Given a protein of interest, PaperBLAST quickly finds similar proteins that are discussed in the literature and presents snippets of text from relevant articles or from the curators. PaperBLAST is available at http://papers.genomics.lbl.gov/.

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Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells

10.1101/238048 ◽

2017 ◽

Cited By ~ 1

Author(s):

Cristina Cruz ◽

Monica Della Rosa ◽

Christel Krueger ◽

Qian Gao ◽

Lucy Field ◽

...

Keyword(s):

Gene Expression ◽

Budding Yeast ◽

Histone H3 ◽

Specific Factor ◽

Protein Coding ◽

Replicative Lifespan ◽

Protein Coding Genes ◽

Genome Wide ◽

Normal Expression ◽

Transcriptional Induction

AbstractTranscription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which deposits di- and tri-methylation on histone H3 lysine 4 (H3K4) to form H3K4me2 and H3K4me3. Here we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations dramatically reduce replicative lifespan and cause widespread gene expression defects. Known repressive functions of H3K4me2 are progressively lost with age, while hundreds of genes become dependent on H3K4me3 for full expression. Induction of these H3K4me3 dependent genes is also impacted in young cells lacking COMPASS components including the H3K4me3-specific factor Spp1. Remarkably, the genome-wide occurrence of H3K4me3 is progressively reduced with age despite widespread transcriptional induction, minimising the normal positive correlation between promoter H3K4me3 and gene expression. Our results provide clear evidence that H3K4me3 is required to attain normal expression levels of many genes across organismal lifespan.

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