cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.21603033
title: Inhibition of mitochondrial complex III or dihydroorotate dehydrogenase (DHODH) triggers formation of poly(A)<sup>+</sup> RNA foci adjacent to nuclear speckles following activation of ATM (ataxia telangiectasia mutated)

description: Intracellular and intercellular signalling networks play an essential role in optimizing cellular homoeostasis and are thought to be partly reflected in nuclear mRNA dynamics. However, the regulation of nuclear mRNA dynamics by intracellular and intercellular signals remains largely unexplored, and research tools are lacking. Through an original screening based on the mRNA metabolic mechanism, we discovered that eight well-known inhibitors cause significant nuclear poly(A)<sup>+</sup> RNA accumulation. Among these inhibitors, we discovered a new mRNA metabolic response in which the addition of antimycin A, an inhibitor of mitochondrial respiratory-chain complex III (complex III), resulted in a marked accumulation of poly(A)<sup>+</sup> RNA near the nuclear speckles. Furthermore, dihydroorotate dehydrogenase (DHODH) inhibitors, a rate-limiting enzyme in the intracellular <i>de novo</i> pyrimidine synthesis reaction that specifically exchanges electrons with complex III, also caused a remarkable accumulation of nuclear poly(A)<sup>+</sup> RNA adjacent to the nuclear speckles, which was abolished by extracellular uridine supply, indicating that the depletion of intracellular pyrimidine affects poly(A)<sup>+</sup> RNA metabolism. Further analysis revealed that ataxia telangiectasia mutated (ATM), a serine and threonine kinase and a master regulator of DNA double-strand break (DSB) and nucleolar stress, is required for this poly(A)<sup>+</sup> RNA nuclear accumulation phenomenon. This study reports new insights into novel aspects of nuclear poly(A)<sup>+</sup> RNA metabolism, especially the relationship between mitochondrial respiratory-chain functions, pyrimidine metabolism, and nuclear RNA metabolism.
DOI: 10.6084/m9.figshare.25458850
title: RefEx2 Datasets for Arabidopsis thaliana Proteome Project

description: RefEx2 is a project to collect, organize, and curate transcriptome datasets of various species as reference resources for gene expression data analysis. It provides 6 reference datasets for four different species: humans, mice, Drosophila melanogaster, and Arabidopsis thaliana. This directory contains the following datasets on Arabidopsis thaliana Proteome Project:ath_proteomeproject_refextable_sample_stats.tsv.gzProcessed data matrixath_proteomeproject_refextable_grouped_sample_desc.tsvGrouped sample descriptionath_proteomeproject_refextable_sampleID_mapping.tsvSample ID mappingsNo. of genes: 32,431<br>No. of samples: 54Key ID: NCBI gene<br>Original data: PRJEB32665<br>Reference(s): DOI: 10.1038/s41586-020-2094-2
DOI: 10.6084/m9.figshare.21603033.v14
title: Inhibition of mitochondrial complex III or dihydroorotate dehydrogenase (DHODH) triggers formation of poly(A)<sup>+</sup> RNA foci adjacent to nuclear speckles following activation of ATM (ataxia telangiectasia mutated)

description: Intracellular and intercellular signalling networks play an essential role in optimizing cellular homoeostasis and are thought to be partly reflected in nuclear mRNA dynamics. However, the regulation of nuclear mRNA dynamics by intracellular and intercellular signals remains largely unexplored, and research tools are lacking. Through an original screening based on the mRNA metabolic mechanism, we discovered that eight well-known inhibitors cause significant nuclear poly(A)<sup>+</sup> RNA accumulation. Among these inhibitors, we discovered a new mRNA metabolic response in which the addition of antimycin A, an inhibitor of mitochondrial respiratory-chain complex III (complex III), resulted in a marked accumulation of poly(A)<sup>+</sup> RNA near the nuclear speckles. Furthermore, dihydroorotate dehydrogenase (DHODH) inhibitors, a rate-limiting enzyme in the intracellular <i>de novo</i> pyrimidine synthesis reaction that specifically exchanges electrons with complex III, also caused a remarkable accumulation of nuclear poly(A)<sup>+</sup> RNA adjacent to the nuclear speckles, which was abolished by extracellular uridine supply, indicating that the depletion of intracellular pyrimidine affects poly(A)<sup>+</sup> RNA metabolism. Further analysis revealed that ataxia telangiectasia mutated (ATM), a serine and threonine kinase and a master regulator of DNA double-strand break (DSB) and nucleolar stress, is required for this poly(A)<sup>+</sup> RNA nuclear accumulation phenomenon. This study reports new insights into novel aspects of nuclear poly(A)<sup>+</sup> RNA metabolism, especially the relationship between mitochondrial respiratory-chain functions, pyrimidine metabolism, and nuclear RNA metabolism.
DOI: 10.6084/m9.figshare.21603033.v13
title: Inhibition of mitochondrial complex III or dihydroorotate dehydrogenase (DHODH) triggers formation of poly(A)<sup>+</sup> RNA foci adjacent to nuclear speckles following activation of ATM (ataxia telangiectasia mutated)

description: Intracellular and intercellular signalling networks play an essential role in optimizing cellular homoeostasis and are thought to be partly reflected in nuclear mRNA dynamics. However, the regulation of nuclear mRNA dynamics by intracellular and intercellular signals remains largely unexplored, and research tools are lacking. Through an original screening based on the mRNA metabolic mechanism, we discovered that eight well-known inhibitors cause significant nuclear poly(A)<sup>+</sup> RNA accumulation. Among these inhibitors, we discovered a new mRNA metabolic response in which the addition of antimycin A, an inhibitor of mitochondrial respiratory-chain complex III (complex III), resulted in a marked accumulation of poly(A)<sup>+</sup> RNA near the nuclear speckles. Furthermore, dihydroorotate dehydrogenase (DHODH) inhibitors, a rate-limiting enzyme in the intracellular <i>de novo</i> pyrimidine synthesis reaction that specifically exchanges electrons with complex III, also caused a remarkable accumulation of nuclear poly(A)<sup>+</sup> RNA adjacent to the nuclear speckles, which was abolished by extracellular uridine supply, indicating that the depletion of intracellular pyrimidine affects poly(A)<sup>+</sup> RNA metabolism. Further analysis revealed that ataxia telangiectasia mutated (ATM), a serine and threonine kinase and a master regulator of DNA double-strand break (DSB) and nucleolar stress, is required for this poly(A)<sup>+</sup> RNA nuclear accumulation phenomenon. This study reports new insights into novel aspects of nuclear poly(A)<sup>+</sup> RNA metabolism, especially the relationship between mitochondrial respiratory-chain functions, pyrimidine metabolism, and nuclear RNA metabolism.
DOI: 10.6084/m9.figshare.21665289
title: Characterization of protein isoform diversity in human umbilical vein endothelial cells via long-read proteogenomics

description: Endothelial cells (ECs) comprise the lumenal lining of all blood vessels and are critical for the functioning of the cardiovascular system. Their phenotypes can be modulated by alternative splicing of RNA to produce distinct protein isoforms. To characterize the RNA and protein isoform landscape within ECs, we applied a long read proteogenomics approach to analyse human umbilical vein endothelial cells (HUVECs). Transcripts delineated from PacBio sequencing serve as the basis for a sample-specific protein database used for downstream mass-spectrometry (MS) analysis to infer protein isoform expression. We detected 53,863 transcript isoforms from 10,426 genes, with 22,195 of those transcripts being novel. Furthermore, the predominant isoform in HUVECs does not correspond with the accepted “reference isoform” 25% of the time, with vascular pathway-related genes among this group. We found 2,597 protein isoforms supported through unique peptides, with an additional 2,280 isoforms nominated upon incorporation of long-read transcript evidence. We characterized a novel alternative acceptor for endothelial-related gene CDH5, suggesting potential changes in its associated signalling pathways. Finally, we identified novel protein isoforms arising from a diversity of RNA splicing mechanisms supported by uniquely mapped novel peptides. Our results represent a high-resolution atlas of known and novel isoforms of potential relevance to endothelial phenotypes and function.
DOI: 10.6084/m9.figshare.21665289.v10
title: Characterization of protein isoform diversity in human umbilical vein endothelial cells via long-read proteogenomics

description: Endothelial cells (ECs) comprise the lumenal lining of all blood vessels and are critical for the functioning of the cardiovascular system. Their phenotypes can be modulated by alternative splicing of RNA to produce distinct protein isoforms. To characterize the RNA and protein isoform landscape within ECs, we applied a long read proteogenomics approach to analyse human umbilical vein endothelial cells (HUVECs). Transcripts delineated from PacBio sequencing serve as the basis for a sample-specific protein database used for downstream mass-spectrometry (MS) analysis to infer protein isoform expression. We detected 53,863 transcript isoforms from 10,426 genes, with 22,195 of those transcripts being novel. Furthermore, the predominant isoform in HUVECs does not correspond with the accepted “reference isoform” 25% of the time, with vascular pathway-related genes among this group. We found 2,597 protein isoforms supported through unique peptides, with an additional 2,280 isoforms nominated upon incorporation of long-read transcript evidence. We characterized a novel alternative acceptor for endothelial-related gene CDH5, suggesting potential changes in its associated signalling pathways. Finally, we identified novel protein isoforms arising from a diversity of RNA splicing mechanisms supported by uniquely mapped novel peptides. Our results represent a high-resolution atlas of known and novel isoforms of potential relevance to endothelial phenotypes and function.
DOI: 10.6084/m9.figshare.18865634
title: A <i>Gypsy</i> element contributes to the nuclear retention and transcriptional regulation of the resident lncRNA in locusts

description: The majority of long noncoding RNAs (lncRNAs) contain transposable elements (TEs). <i>PAHAL</i>, a nuclear-retained lncRNA that is inserted by a <i>Gypsy</i> retrotransposon, has been shown to be a vital regulator of phenylalanine hydroxylase (<i>PAH</i>) gene expression that controls dopamine biosynthesis and behavioural aggregation in the migratory locust. However, the role of the <i>Gypsy</i> retrotransposon in the transcriptional regulation of <i>PAHAL</i> remains unknown. Here, we identified a <i>Gypsy</i> retrotransposon (named <i>Gypsy</i> element) as an inverted long terminal repeat located in the 3′ end of <i>PAHAL</i>, representing a feature shared by many other lncRNAs in the locust genome. The embedded <i>Gypsy</i> element contains a RNA nuclear localization signal motif, which promotes the stable accumulation of <i>PAHAL</i> in the nucleus. The <i>Gypsy</i> element also provides high-affinity SRSF2 binding sites for <i>PAHAL</i> that induce the recruitment of SRSF2, resulting in the <i>PAHAL</i>-mediated transcriptional activation of <i>PAH</i>. Thus, our data demonstrate that TEs provide discrete functional domains for lncRNA organization and highlight the contribution of TEs to the regulatory significance of lncRNAs.
DOI: 10.6084/m9.figshare.18865634.v1
title: A <i>Gypsy</i> element contributes to the nuclear retention and transcriptional regulation of the resident lncRNA in locusts

description: The majority of long noncoding RNAs (lncRNAs) contain transposable elements (TEs). <i>PAHAL</i>, a nuclear-retained lncRNA that is inserted by a <i>Gypsy</i> retrotransposon, has been shown to be a vital regulator of phenylalanine hydroxylase (<i>PAH</i>) gene expression that controls dopamine biosynthesis and behavioural aggregation in the migratory locust. However, the role of the <i>Gypsy</i> retrotransposon in the transcriptional regulation of <i>PAHAL</i> remains unknown. Here, we identified a <i>Gypsy</i> retrotransposon (named <i>Gypsy</i> element) as an inverted long terminal repeat located in the 3′ end of <i>PAHAL</i>, representing a feature shared by many other lncRNAs in the locust genome. The embedded <i>Gypsy</i> element contains a RNA nuclear localization signal motif, which promotes the stable accumulation of <i>PAHAL</i> in the nucleus. The <i>Gypsy</i> element also provides high-affinity SRSF2 binding sites for <i>PAHAL</i> that induce the recruitment of SRSF2, resulting in the <i>PAHAL</i>-mediated transcriptional activation of <i>PAH</i>. Thus, our data demonstrate that TEs provide discrete functional domains for lncRNA organization and highlight the contribution of TEs to the regulatory significance of lncRNAs.
DOI: 10.6084/m9.figshare.21665289.v9
title: Characterization of protein isoform diversity in human umbilical vein endothelial cells via long-read proteogenomics

description: Endothelial cells (ECs) comprise the lumenal lining of all blood vessels and are critical for the functioning of the cardiovascular system. Their phenotypes can be modulated by alternative splicing of RNA to produce distinct protein isoforms. To characterize the RNA and protein isoform landscape within ECs, we applied a long read proteogenomics approach to analyse human umbilical vein endothelial cells (HUVECs). Transcripts delineated from PacBio sequencing serve as the basis for a sample-specific protein database used for downstream mass-spectrometry (MS) analysis to infer protein isoform expression. We detected 53,863 transcript isoforms from 10,426 genes, with 22,195 of those transcripts being novel. Furthermore, the predominant isoform in HUVECs does not correspond with the accepted “reference isoform” 25% of the time, with vascular pathway-related genes among this group. We found 2,597 protein isoforms supported through unique peptides, with an additional 2,280 isoforms nominated upon incorporation of long-read transcript evidence. We characterized a novel alternative acceptor for endothelial-related gene CDH5, suggesting potential changes in its associated signalling pathways. Finally, we identified novel protein isoforms arising from a diversity of RNA splicing mechanisms supported by uniquely mapped novel peptides. Our results represent a high-resolution atlas of known and novel isoforms of potential relevance to endothelial phenotypes and function.
DOI: 10.6084/m9.figshare.19361753
title: Difficulties translating antisense-mediated activation of Frataxin expression from cell culture to mice

description: Friedreich’s ataxia (FA) is an inherited neurodegenerative disorder caused by decreased expression of frataxin (FXN) protein. Previous studies have shown that antisense oligonucleotides (ASOs) and single-stranded silencing RNAs can be used to increase expression of frataxin in cultured patient-derived cells. In this study, we investigate the potential for oligonucleotides to increase frataxin expression in a mouse model for FA. After confirming successful <i>in vivo</i> delivery of oligonucleotides using a benchmark gapmer targeting the nuclear noncoding RNA Malat1, we tested anti-<i>FXN</i> oligonucleotides designed to function by various mechanisms. None of these strategies yielded enhanced expression of <i>FXN</i> in the model mice. Our inability to translate activation of <i>FXN</i> expression from cell culture to mice may be due to inadequate potency of our compounds or differences in the molecular mechanisms governing <i>FXN</i> gene repression and activation in FA model mice.
DOI: 10.6084/m9.figshare.19361753.v1
title: Difficulties translating antisense-mediated activation of Frataxin expression from cell culture to mice

description: Friedreich’s ataxia (FA) is an inherited neurodegenerative disorder caused by decreased expression of frataxin (FXN) protein. Previous studies have shown that antisense oligonucleotides (ASOs) and single-stranded silencing RNAs can be used to increase expression of frataxin in cultured patient-derived cells. In this study, we investigate the potential for oligonucleotides to increase frataxin expression in a mouse model for FA. After confirming successful <i>in vivo</i> delivery of oligonucleotides using a benchmark gapmer targeting the nuclear noncoding RNA Malat1, we tested anti-<i>FXN</i> oligonucleotides designed to function by various mechanisms. None of these strategies yielded enhanced expression of <i>FXN</i> in the model mice. Our inability to translate activation of <i>FXN</i> expression from cell culture to mice may be due to inadequate potency of our compounds or differences in the molecular mechanisms governing <i>FXN</i> gene repression and activation in FA model mice.
DOI: 10.6084/m9.figshare.21786363
title: Bioinformatics analysis and the association of polymorphisms within the caprine <i>GDF9</i> gene promoter with economically useful traits in Damani goats

description: The blood sample from 60 Damani does were collected and genomic DNA was extracted, and DNA integrity were investigated. A 447 bp promoter fragment of the <i>GDF9</i> gene was amplified and Sanger sequenced for the identification of <i>GDF9</i> gene polymorphism. Three novel SNPs were identified at positions g. 97(T &gt; A), g. 142 (G &gt; G) and g. 313(C &gt; T) in the promoter region of the caprine <i>GDF9</i> gene which significantly (<i>P</i> &lt; 0.05) influenced litter size, body measurement, and milk production traits in Damani goats. The genotype CT of SNP1 significantly (<i>P</i> &lt; 0.05) improved litter size, genotype GG of SNP2 significantly (<i>P</i> &lt; 0.05) enhanced milk production, while the genotypes CC of SNP3 significant (<i>P</i> &lt; 0.05) increased body measurement traits in Damani goats. Moreover, in SNP1 loss of 3 transcription factors (TF) binding sites occurred, SNP2 caused loss of two TFs binding sites, and SNP3 caused loss of a single TF binding site. Similarly, SNP1 and SNP2 caused the gain of three new potential TF binding sites, and SNP3 caused gain of two new TF binding sites. It is concluded that caprine <i>GDF9</i> gene could be used as a candidate gene for litter size, milk production and body measurement traits in Damani goats through marker-assisted selection for future breeding program.
DOI: 10.6084/m9.figshare.21786363.v1
title: Bioinformatics analysis and the association of polymorphisms within the caprine <i>GDF9</i> gene promoter with economically useful traits in Damani goats

description: The blood sample from 60 Damani does were collected and genomic DNA was extracted, and DNA integrity were investigated. A 447 bp promoter fragment of the <i>GDF9</i> gene was amplified and Sanger sequenced for the identification of <i>GDF9</i> gene polymorphism. Three novel SNPs were identified at positions g. 97(T &gt; A), g. 142 (G &gt; G) and g. 313(C &gt; T) in the promoter region of the caprine <i>GDF9</i> gene which significantly (<i>P</i> &lt; 0.05) influenced litter size, body measurement, and milk production traits in Damani goats. The genotype CT of SNP1 significantly (<i>P</i> &lt; 0.05) improved litter size, genotype GG of SNP2 significantly (<i>P</i> &lt; 0.05) enhanced milk production, while the genotypes CC of SNP3 significant (<i>P</i> &lt; 0.05) increased body measurement traits in Damani goats. Moreover, in SNP1 loss of 3 transcription factors (TF) binding sites occurred, SNP2 caused loss of two TFs binding sites, and SNP3 caused loss of a single TF binding site. Similarly, SNP1 and SNP2 caused the gain of three new potential TF binding sites, and SNP3 caused gain of two new TF binding sites. It is concluded that caprine <i>GDF9</i> gene could be used as a candidate gene for litter size, milk production and body measurement traits in Damani goats through marker-assisted selection for future breeding program.
DOI: 10.6084/m9.figshare.22109035
title: Assessment of genetic diversity of the fat-tailed Dumba sheep of India by mitochondrial and microsatellite markers

description: India has a centuries-old tradition of sheep production and breeding that accomplish economic, agricultural, and religious roles. In addition to the 44 registered sheep breeds, there is a fat-tailed sheep population referred to as Dumba. This study evaluated genetic variation in Dumba sheep and its differentiation from other Indian sheep breeds using mitochondrial DNA and genomic microsatellite loci. Haplotype and nucleotide diversity based on mitochondrial DNA analysis revealed substantially high maternal genetic diversity in Dumba sheep. Major ovine haplogroups A and B observed in sheep populations across the globe registered their presence in the Dumba sheep. The molecular genetic analysis using microsatellite markers also showed high measures of allele (10.125 ± 0.762) and gene diversity (0.749 ± 0.029). Results correspond to the non-bottleneck population that is near mutation-drift equilibrium despite some deficiency in the number of heterozygotes (F<sub>IS</sub> = 0.043 ± 0.059). Phylogenetic clustering confirmed Dumba to be a distinct population. Results of this study endow authorities with critical information imperative for sustainable utilization and conservation of Indian fat-tailed sheep, which is considered to be an untapped genetic resource contributing to the food security, livelihood, and economic sustainability of rural households in marginal areas of the country.
DOI: 10.6084/m9.figshare.22109035.v1
title: Assessment of genetic diversity of the fat-tailed Dumba sheep of India by mitochondrial and microsatellite markers

description: India has a centuries-old tradition of sheep production and breeding that accomplish economic, agricultural, and religious roles. In addition to the 44 registered sheep breeds, there is a fat-tailed sheep population referred to as Dumba. This study evaluated genetic variation in Dumba sheep and its differentiation from other Indian sheep breeds using mitochondrial DNA and genomic microsatellite loci. Haplotype and nucleotide diversity based on mitochondrial DNA analysis revealed substantially high maternal genetic diversity in Dumba sheep. Major ovine haplogroups A and B observed in sheep populations across the globe registered their presence in the Dumba sheep. The molecular genetic analysis using microsatellite markers also showed high measures of allele (10.125 ± 0.762) and gene diversity (0.749 ± 0.029). Results correspond to the non-bottleneck population that is near mutation-drift equilibrium despite some deficiency in the number of heterozygotes (F<sub>IS</sub> = 0.043 ± 0.059). Phylogenetic clustering confirmed Dumba to be a distinct population. Results of this study endow authorities with critical information imperative for sustainable utilization and conservation of Indian fat-tailed sheep, which is considered to be an untapped genetic resource contributing to the food security, livelihood, and economic sustainability of rural households in marginal areas of the country.