scholarly journals Genome-wide analysis of consistently RNA edited sites in human blood reveals interactions with mRNA processing genes and suggests correlations with cell types and biological variables

2018 ◽  
Author(s):  
Edoardo Giacopuzzi ◽  
Massimo Gennarelli ◽  
Chiara Sacco ◽  
Alice Filippini ◽  
Jessica Mingardi ◽  
...  
Keyword(s):  
Rna Editing ◽  
Human Blood ◽  
Cell Types ◽  
Small Region ◽  
Rna Seq ◽  
Biological Variables ◽  
Genome Wide ◽  
Genes Encoding ◽  
Editing Process ◽  
Detailed Picture

AbstractBackgroundA-to-I RNA editing is a co-/post-transcriptional modification catalyzed by ADAR enzymes, that deaminates Adenosines (A) into Inosines (I). Most of known editing events are located within inverted ALU repeats, but they also occur in coding sequences and may alter the function of encoded proteins. RNA editing contributes to generate transcriptomic diversity and it is found altered in cancer, autoimmune and neurological disorders. Emerging evidences indicate that editing process could be influenced by genetic variations, biological and environmental variables.ResultsWe analyzed RNA editing levels in human blood using RNA-seq data from 459 healthy individuals and identified 2,079 sites consistently edited in this tissue. As expected, analysis of gene expression revealed thatADARis the major contributor to editing on these sites, explaining ∼13% of observed variability. After removingADAReffect, we found significant associations for 1,122 genes, mainly involved in RNA processing. These genes were significantly enriched in genes encoding proteins interacting with ADARs, including 276 potential ADARs interactors and 9 ADARs direct partners. In addition, our analysis revealed several factors potentially influencing RNA editing in blood, including cell composition, age, Body Mass Index, smoke and alcohol consumption. Finally, we identified genetic loci associated with editing levels, including knownADAReQTLs and a small region on chromosome 7, containingLOC730338,a lincRNA gene that appears to modulate ADARs mRNA expression.ConclusionsOur data provides a detailed picture of the most relevant RNA editing events and their variability in human blood, giving interesting insights on potential mechanisms behind this post-transcriptional modification and its regulation in this tissue.

scholarly journals Genome-Wide Analysis of Multiple Organellar RNA Editing Factor (MORF) Family in Kiwifruit (Actinidia chinensis) Reveals Its Roles in Chloroplast RNA Editing and Pathogens Stress

Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 146
Author(s):  
Yuhong Xiong ◽  
Jing Fang ◽  
Xiaohan Jiang ◽  
Tengfei Wang ◽  
Kangchen Liu ◽  
...  
Keyword(s):  
Rna Editing ◽  
Chloroplast Development ◽  
Structural Features ◽  
Resistance Mechanisms ◽  
Actinidia Chinensis ◽  
Rna Seq ◽  
Good Taste ◽  
Genome Wide ◽  
Solid Foundation ◽  
Chloroplast Rna

Kiwifruit (Actinidia chinensis) is well known for its high vitamin C content and good taste. Various diseases, especially bacterial canker, are a serious threat to the yield of kiwifruit. Multiple organellar RNA editing factor (MORF) genes are pivotal factors in the RNA editosome that mediates Cytosine-to-Uracil RNA editing, and they are also indispensable for the regulation of chloroplast development, plant growth, and response to stresses. Although the kiwifruit genome has been released, little is known about MORF genes in kiwifruit at the genome-wide level, especially those involved in the response to pathogens stress. In this study, we identified ten MORF genes in the kiwifruit genome. The genomic structures and chromosomal locations analysis indicated that all the MORF genes consisted of three conserved motifs, and they were distributed widely across the seven linkage groups and one contig of the kiwifruit genome. Based on the structural features of MORF proteins and the topology of the phylogenetic tree, the kiwifruit MORF gene family members were classified into six groups (Groups A–F). A synteny analysis indicated that two pairs of MORF genes were tandemly duplicated and five pairs of MORF genes were segmentally duplicated. Moreover, based on analysis of RNA-seq data from five tissues of kiwifruit, we found that both expressions of MORF genes and chloroplast RNA editing exhibited tissue-specific patterns. MORF2 and MORF9 were highly expressed in leaf and shoot, and may be responsible for chloroplast RNA editing, especially the ndhB genes. We also observed different MORF expression and chloroplast RNA editing profiles between resistant and susceptible kiwifruits after pathogen infection, indicating the roles of MORF genes in stress response by modulating the editing extend of mRNA. These results provide a solid foundation for further analyses of the functions and molecular evolution of MORF genes, in particular, for clarifying the resistance mechanisms in kiwifruits and breeding new cultivars with high resistance.

scholarly journals Regulation of DNA methylation on key parasitism genes of Cysticercus cellulosae revealed by integrative epigenomic-transcriptomic analyses

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Xinrui Wang ◽  
Weiyi Song ◽  
Guanyu Ji ◽  
Yining Song ◽  
Xiaolei Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Developmental Regulation ◽  
Taenia Solium ◽  
Rna Seq ◽  
Host Interactions ◽  
Genome Wide ◽  
Cysticercus Cellulosae ◽  
Genes Encoding ◽  
Genome Bisulfite Sequencing ◽  
Parasitism Genes

Abstract Background The life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions. Result In the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.

scholarly journals DeeReCT-TSS: A novel meta-learning-based method annotates TSS in multiple cell types based on DNA sequences and RNA-seq data

2021 ◽  
Author(s):  
Juexiao Zhou ◽  
Bin Zhang ◽  
Haoyang Li ◽  
Longxi Zhou ◽  
Zhongxiao Li ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Rna Seq ◽  
Sources Of Information ◽  
Genome Wide ◽  
A Genome ◽  
Meta Learning ◽  
Multiple Cell ◽  
Different Cell Types ◽  
Genome Scale

The accurate annotation of TSSs and their usage is critical for the mechanistic understanding of gene regulation under different biological contexts. To fulfill this, specific high-throughput experimental technologies have been developed to capture TSSs in a genome-wide manner. Various computational tools have also been developed for in silico prediction of TSSs solely based on genomic sequences. Most of these tools have drastic false positive predictions when applied on the genome-scale. Here, we present DeeReCT-TSS, a deep-learning-based method that is capable of TSSs identification across the whole genome based on DNA sequences and conventional RNA-seq data. We show that by effectively incorporating these two sources of information, DeeReCT-TSS significantly outperforms other solely sequence-based methods on the precise annotation of TSSs used in different cell types. Furthermore, we develop a meta-learning-based extension for simultaneous transcription start site (TSS) annotation on 10 cell types, which enables the identification of cell-type-specific TSS. Finally, we demonstrate the high precision of DeeReCT-TSS on two independent datasets from the ENCODE project by correlating our predicted TSSs with experimentally defined TSS chromatin states.

scholarly journals Genome-Wide Identification of U-To-C RNA Editing Events for Nuclear Genes in Arabidopsis thaliana

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 635
Author(s):  
Ruchika ◽  
Chisato Okudaira ◽  
Matomo Sakari ◽  
Toshifumi Tsukahara
Keyword(s):  
Rna Editing ◽  
Sanger Sequencing ◽  
Developmental Stages ◽  
Nuclear Genes ◽  
Rna Seq ◽  
Pentatricopeptide Repeat ◽  
Stages Of Growth ◽  
Genome Wide ◽  
Ppr Genes ◽  
Plant Organelles

Cytosine-to-Uridine (C-to-U) RNA editing involves the deamination phenomenon, which is observed in animal nucleus and plant organelles; however, it has been considered the U-to-C is confined to the organelles of limited non-angiosperm plant species. Although previous RNA-seq-based analysis implied U-to-C RNA editing events in plant nuclear genes, it has not been broadly accepted due to inadequate confirmatory analyses. Here we examined the U-to-C RNA editing in Arabidopsis tissues at different developmental stages of growth. In this study, the high-throughput RNA sequencing (RNA-seq) of 12-day-old and 20-day-old Arabidopsis seedlings was performed, which enabled transcriptome-wide identification of RNA editing sites to analyze differentially expressed genes (DEGs) and nucleotide base conversions. The results showed that DEGs were expressed to higher levels in 12-day-old seedlings than in 20-day-old seedlings. Additionally, pentatricopeptide repeat (PPR) genes were also expressed at higher levels, as indicated by the log2FC values. RNA-seq analysis of 12-day- and 20-day-old Arabidopsis seedlings revealed candidates of U-to-C RNA editing events. Sanger sequencing of both DNA and cDNA for all candidate nucleotide conversions confirmed the seven U-to-C RNA editing sites. This work clearly demonstrated presence of U-to-C RNA editing for nuclear genes in Arabidopsis, which provides the basis to study the mechanism as well as the functions of the unique post-transcriptional modification.

scholarly journals Regulation of DNA Methylation on Key Parasitism Genes of Cysticercus Cellulosae Revealed by Integrative Epigenomic-Transcriptomic Analyses

2020 ◽  
Author(s):  
Xinrui Wang ◽  
Weiyi Song ◽  
Yining Song ◽  
Guanyu Ji ◽  
Xuenong Luo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Developmental Regulation ◽  
Taenia Solium ◽  
Rna Seq ◽  
Host Interactions ◽  
Genome Wide ◽  
Cysticercus Cellulosae ◽  
Genes Encoding ◽  
Genome Bisulfite Sequencing ◽  
Parasitism Genes

Abstract Background: The life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions.Result: In the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.

scholarly journals Genome-Wide Transcriptomic Analysis of N-Caproic Acid Production in Ruminococcaceae Bacterium CPB6 with Lactate Supplementation

2020 ◽  
Author(s):  
YONG TAO ◽  
Shaowen Lu ◽  
Yi Wang ◽  
Cuicui Wei
Keyword(s):  
Expression Patterns ◽  
Caproic Acid ◽  
Transcriptional Analysis ◽  
Transcriptional Level ◽  
Rna Seq ◽  
Phosphotransferase System ◽  
Oxidation Pathway ◽  
Genome Wide ◽  
Genes Encoding ◽  
Substrate Binding Protein

Abstract Background: n-Caproic acid (CA) is gaining increased attention due to its high value as a chemical feedstock. Our recent studies have demonstrated that lactate can be an attractive energy substrate for the production of CA. However, little is known about the potential molecular mechanism for CA production triggered by the supplementation of exogenous lactate at the gene transcriptional level. Results: 5% lactate was supplemented into the fermentation with Ruminococcaceae bacterium CPB6 for CA production. Results showed that lactate supplementation led to earlier CA production and higher final CA titer and productivity. Transcriptional analysis was carried out using RNA-Seq for the culture with lactate supplementation compared to the control (without lactate supplementation). It has been indicated that there were only 34 differentially expressed genes (DEGs) between the two groups at the exponential phase, of which 15 were upregulated, and 19 were downregulated by more than two-fold. A total of 245 DEGs were identified between the two groups at the stationary phase, of which 123 were upregulated and 122 were downregulated. These DEGs cover crucial functional categories. Specifically, 5 genes responsible for the reverse β-oxidation pathway, 11 genes encoding ATP-binding cassette (ABC) transporters, 6 genes encoding substrate-binding protein (SBP) and 4 genes encoding phosphotransferase system (PTS) transporters were strikingly upregulated in response to the addition of lactate. These genes would be candidates for future studies aiming at understanding the regulatory mechanism of lactate conversion into CA, as well as for the improvement of CA production in strain CPB6. Conclusion: This study suggested that lactate supplementation can promote CA production by altering the expression patterns of genes involved in the essential metabolic pathways, such as central pyruvate metabolism, the reverse β-oxidation pathway, ABC and PTS transports. The findings presented herein reveal unique insights into the biomolecular effects of lactate on CA production at the gene transcriptional level.

scholarly journals RNA-seq highlights parallel and contrasting patterns in the evolution of the nuclear genome of holo-mycoheterotrophic plants

2017 ◽  
Author(s):  
M.I. Schelkunov ◽  
A.A. Penin ◽  
M.D. Logacheva
Keyword(s):  
Protein Import ◽  
Nuclear Genome ◽  
Nuclear Gene ◽  
Nuclear Genes ◽  
Rna Seq ◽  
Nucleotide Substitutions ◽  
Plastid Genomes ◽  
Genome Wide ◽  
Genes Encoding ◽  
Mycoheterotrophic Plants

Summary• While photosynthesis is the most notable trait of plants, several lineages of plants (so-called holo-heterotrophs) have adapted to obtain organic compounds from other sources. The switch to heterotrophy leads to profound changes at the morphological, physiological and genomic levels.• Here, we characterize the transcriptomes of three species representing two lineages of mycoheterotrophic plants: orchids (Epipogium aphyllum and Epipogium roseum) and Ericaceae (Hypopitys monotropa). Comparative analysis is used to highlight the parallelism between distantly related holo-heterotrophic plants.• In both lineages, we observed genome-wide elimination of nuclear genes that encode proteins related to photosynthesis, while systems associated with protein import to plastids as well as plastid transcription and translation remain active. Genes encoding components of plastid ribosomes that have been lost from the plastid genomes have not been transferred to the nuclear genomes; instead, some of the encoded proteins have been substituted by homologs. The nuclear genes of both Epipogium species accumulated mutations twice as rapidly as their photosynthetic relatives; in contrast, no increase in the substitution rate was observed in H.monotropa.• Holo-heterotrophy leads to profound changes in nuclear gene content. The observed increase in the rate of nucleotide substitutions is lineage specific, rather than a universal phenomenon among non-photosynthetic plants.

scholarly journals Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

2021 ◽  
Author(s):  
Heidi Hautakangas ◽  
Bendik S. Winsvold ◽  
Sanni E. Ruotsalainen ◽  
Gyda Bjornsdottir ◽  
Aster V. E. Harder ◽  
...  
Keyword(s):  
Migraine With Aura ◽  
Drug Targets ◽  
Migraine Without Aura ◽  
Genome Wide Association Study ◽  
Cell Types ◽  
Tissue Cell ◽  
Risk Alleles ◽  
Genetic Components ◽  
Genome Wide ◽  
Genes Encoding

AbstractMigraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. This genome-wide association study (GWAS) of 102,084 migraine cases and 771,257 controls identified 123 loci of which 86 are novel. The loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. A stratification of the risk loci using 29,679 cases with subtype information, of which approximately half have never been used in a GWAS before, indicated three risk variants that appear specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that appear specific for migraine without aura (near SPINK2 and near FECH), and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.

scholarly journals Quantification of differential transcription factor activity and multiomics-based classification into activators and repressors:diffTF

2018 ◽  
Author(s):  
Ivan Berest ◽  
Christian Arnold ◽  
Armando Reyes-Palomares ◽  
Giovanni Palla ◽  
Kasper Dindler Rasmussen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Case Studies ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Lymphocytic Leukemia ◽  
Transcriptional Activators ◽  
Rna Seq ◽  
Data Set ◽  
Genome Wide

Transcription factor (TF) activity is an important read-out of cellular signalling pathways and thus to assess regulatory differences across conditions. However, current technologies lack the ability to simultaneously assess activity changes for multiple TFs and in particular to determine whether a specific TF acts globally as transcriptional repressor or activator. To this end, we introduce a widely applicable genome-wide methoddiffTFto assess differential TF activity and to classify TFs as activator or repressor (available athttps://git.embl.de/grp-zaugg/diffTF). This is done by integrating any type of genome-wide chromatin accessibility data with RNA-Seq data and in-silico predicted TF binding sites. We corroborated the classification of TFs into repressors and activators by three independent analyses based on enrichments of active/repressive chromatin states, correlation of TF activity with gene expression, and activator-and repressor-specific chromatin footprints. To show the power ofdiffTF, we present two case studies: First, we applieddiffTFin to a large ATAC-Seq/RNA-Seq dataset comparing mutated and unmutated chronic lymphocytic leukemia samples, where we identified dozens of known (40%) and potentially novel (60%) TFs that are differentially active. We were also able to classify almost half of them as either repressor and activator. Second, we applieddiffTFto a small ATAC-Seq/RNA-Seq data set comparing two cell types along the hematopoietic differentiation trajectory (multipotent progenitors – MPP – versus granulocyte-macrophage progenitors – GMP). Here we identified the known drivers of differentiation and found that the majority of the differentially active TFs are transcriptional activators. Overall,diffTFwas able to recover the known TFs in both case studies, additionally identified TFs that have been less well characterized in the given condition, and provides a classification of the TFs into transcriptional activators and repressors.

Sign in / Sign up

Export Citation Format

Share Document