Biology subjects

Zhou, C.

Publications and source records attributed to Zhou, C..

16 recordsLinked to original sources

bioRxiv2018

Differential gene expression, including Sjfs800, in Schistosoma japonicum females before, during, and after male-female pairing

Schistosomiasis is a prevalent but neglected tropical disease caused by parasitic trematodes of the genus Schistosoma, with the primary disease-causing species being S. haematobium, S. mansoni, and S. japonicum. Male-female pairing of schistosomes is necessary for sexual maturity and the production of a large number of eggs, which are primarily responsible for schistosomiasis dissemination and pathology. Here, we used microarray hybridization, bioinformatics, quantitative PCR, in situ hybridization, and gene silencing assays to identify genes that play critical roles in S. japonicum reproduction biology, particularly in vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. Microarray hybridization analyses generated a comprehensive set of genes differentially transcribed before and after male-female pairing. Although the transcript profiles of females were similar 16 and 18 days after host infection, marked gene expression changes were observed at 24 days. The 30 most abundantly transcribed genes on day 24 included those associated with vitellarium development. Among these, genes for female-specific 800 (fs800), eggshell precursor protein, and superoxide dismutase (cu-zn-SOD) were substantially upregulated. Our in situ hybridization results in female S. japonicum indicated that cu-zn-SOD mRNA was highest in the ovary and vitellarium, eggshell precursor protein mRNA was expressed in the ovary, ootype, and vitellarium, and Sjfs800 mRNA was observed only in the vitellarium, localized in mature vitelline cells. Knocking down the Sjfs800 gene in female S. japonicum by approximately 60% reduced the number of mature vitelline cells, decreased rates of pairing and oviposition, and decreased the number of eggs produced in each male-female pairing by about 50%. These results indicate that Sjfs800 is essential for vitellarium development and egg production in S. japonicum and suggest that Sjfs800 regulation may provide a novel approach for the prevention or treatment of schistosomiasis.\n\nAuthor SummarySchistosomiasis is a common but largely unstudied tropical disease caused by parasitic trematodes of the genus Schistosoma. The eggs of schistosomes are responsible for schistosomiasis transmission and pathology, and the production of these eggs is dependent on the pairing of females and males. In this study, we determined which genes in Schistosoma japonicum females were differentially expressed before and after pairing with males, identifying the 30 most abundantly expressed of these genes. Among these 30 genes, we further characterized those in female S. japonicum that were upregulated after pairing and that were related to reproduction and vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. We identified three such genes, S. japonicum female-specific 800 (Sjfs800), eggshell precursor protein, and superoxide dismutase, and confirmed that the mRNAs for these genes were primarily localized in reproductive structures. By using gene silencing techniques to reduce the amount of Sjfs800 mRNA in females by about 60%, we determined that Sjfs800 plays a key role in development of the vitellarium and egg production. This finding suggests that regulation of Sjfs800 may provide a novel approach to reduce egg counts and thus aid in the prevention or treatment of schistosomiasis.

genomics↗

bioRxiv2018

Tenuivirus uses a molecular bridge strategy to overcome insect midgut barriers for virus persistent transmission

Many persistent transmitted plant viruses, including Rice stripe tenuivirus (RSV), cause serious damages to crop productions in China and worldwide. Although many reports have indicated that successful insect-mediated virus transmission depends on proper virus-insect vector interactions, the mechanism(s) controlling interactions between viruses and insect vectors for virus persistent transmission remained poorly understood. In this study, we used RSV and its small brown planthopper (SBPH) vector as a working model to elucidate the molecular mechanism controlling RSV virion entrance into SBPH midgut for persistent transmission. We have now demonstrated that this non-enveloped Tenuivirus uses its non-structural glycoprotein NSvc2 as a helper component to bridge the specific interaction between virion and SBPH midgut cells, leading to overcome SBPH midgut barriers for virus persistent transmission. In the absence of this glycoprotein, purified RSV virion is not capable of entering SBPH midgut cells. In RSV-infected cells, glycoprotein NSvc2 is processed into two mature proteins: an amino-terminal protein NSvc2-N and a carboxyl-terminal protein NSvc2-C. We determined that NSvc2-N interacted with RSV virion and bound directly to midgut lumen surface via its N-glycosylation sites. Upon recognition by midgut cells, the midgut cells underwent endocytosis followed by compartmentalizing RSV virion and NSvc2 into early and then late endosomes. The acidic condition inside the late endosome triggered conformation change of NSvc2-C and caused cell membrane fusion via its highly conserved fusion loop motifs, leading to the release of RSV virion from endosome into cytosol. In summary, our results showed for the first time that a rice Tenuivirus uses a molecular bridge strategy to ensure proper interactions between virus and insect midgut for successful persistent transmission.\n\nAuthor summaryOver 75% of the known plant viruses are insect transmitted. Understanding how plant viruses interacted with their insect vectors during virus transmission is one of the key steps to manage virus diseases worldwide. Both the direct and indirect virus-insect vector interaction models have been proposed for virus non-persistent and semi-persistent transmission. However, the indirect virus-vector interaction mechanism during virus persistent transmission has not been reported previously. In this study, we developed a new reverse genetics technology and demonstrated that the circulative and propagative transmitted Rice stripe tenuivirus utilizes a glycoprotein NSvc2 as a helper component to ensure a specific interaction between Tenuivirus virion and midgut cells of small brown planthopper (SBPH), leading to conquering the midgut barrier of SBPH. This is the first report of a helper component mediated-molecular bridge mechanism for virus persistent transmission. These new findings and our new model on persistent transmission expand our understanding of molecular mechanism(s) controlling virus-insect vector interactions during virus transmission in nature.

pathology↗

bioRxiv2018

Neuroglial Remodeling After Various Ocular Injuries is Regulated by Microglia

Reactive microglia and infiltrating peripheral monocytes have been implicated in many neurodegenerative diseases of the retina and central nervous system (CNS). However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral monocytes that infiltrate the retina after ocular injury in mice become permanently engrafted into the tissue, establishing a pro-inflammatory phenotype that promotes neurodegeneration. Here, we show in mice that microglia regulate the process of neuroglia remodeling during ocular injury, and their depletion results in marked upregulation of inflammatory markers, such as Il17f, Tnfsf11, Ccl4, Il1a, Ccr2, Il4, Il5, and Csf2 in the retina, abnormal engraftment of peripheral CCR2+ CX3CR1+ monocytes into the retina and is associated with increased retinal ganglion cell (RGC) loss, retinal nerve fiber layer thinning, and RPE65+ cell migration onto the retinal surface. Furthermore, we show that other types of ocular injuries, such as penetrating corneal trauma and ocular hypertension, also cause similar changes. However, optic nerve crush injury mediated RGC loss evokes neither peripheral monocyte response in the retina, nor RPE65+ cell migration, although peripheral CX3CR1+ and CCR2+ monocytes infiltrate the optic nerve injury site and remain present for months. Our study suggests that microglia are key regulators of peripheral monocyte infiltration and RPE migration and their depletion results in abnormal neuroglia remodeling that exacerbates neuroretinal tissue damage. This mechanism of retinal damage through neuroglia remodeling may be clinically important for the treatment of patients with ocular injuries, including surgical traumas.

immunology↗

bioRxiv2018

RBM-5 modulates U2AF large subunit-dependent alternative splicing in C. elegans

A key step in pre-mRNA splicing is the recognition of 3 splicing sites by the U2AF large and small subunits, a process regulated by numerous trans-acting splicing factors. How these trans-acting factors interact with U2AF in vivo is unclear. From a screen for suppressors of the temperature-sensitive (ts) lethality of the C. elegans U2AF large subunit gene uaf-1(n4588) mutants, we identified mutations in the RNA binding motif gene rbm-5, a homolog of the tumor suppressor RBM5. rbm-5 mutations can suppress uaf-1(n4588) ts-lethality by loss of function and neuronal expression of rbm-5 was sufficient to rescue the suppression. Transcriptome analyses indicate that uaf-1(n4588) affected the expression of numerous genes and rbm-5 mutations can partially reverse the abnormal gene expression to levels similar to that of wild type. Though rbm-5 mutations did not obviously affect alternative splicing per se, they can suppress or enhance, in a gene-specific manner, the altered splicing of genes in uaf-1(n4588) mutants. Specifically, the recognition of a weak 3 splice site was more susceptible to the effect of rbm-5. Our findings provide novel in vivo evidence that RBM-5 can modulate UAF-1-dependent RNA splicing and suggest that RBM5 might interact with U2AF large subunit to affect tumor formation.\n\nAuthor summaryRNA splicing is a critical regulatory step for eukaryotic gene expression and has been involved in the pathogenesis of multiple diseases. How RNA splicing factors interact in vivo to affect the splicing and expression of genes is unclear. In studying the temperature-sensitive lethal phenotypes of a mutation affecting the splicing factor U2AF large subunit gene uaf-1 in the nematode Caenorhabditis elegans, we isolated suppressive mutations in the rbm-5 gene, a homolog of the human tumor suppressor gene RBM5. rbm-5 is broadly expressed in neurons to enhance the lethality of the uaf-1 mutants. We found that the uaf-1 mutation causes aberrant expression of genes in numerous biological pathways, a large portion of which can be corrected by rbm-5 mutations. The abnormal splicing of multiple genes caused by the uaf-1 mutation is either corrected or enhanced by rbm-5 mutations in a gene-specific manner. We propose that RBM-5 interacts with UAF-1 to affect RNA splicing and the tumor suppressor function of RBM5 might involve U2AF-dependent RNA splicing.

genetics↗

bioRxiv2018

Permanent neuroglial remodeling of the retina following infiltration of CSF1R-inhibition resistant peripheral monocytes.

Previous studies have demonstrated that ocular injury can lead to prompt infiltration of bone marrow-derived peripheral monocytes into the retina. However, the ability of these cells to integrate into the tissue and become microglia has not been studied. Here we show that such peripheral monocytes not only infiltrate into the retina after ocular injury, but that they engraft permanently, migrate to the three distinct microglia strata, and adopt a microglia-like morphology. However, contrary to the original microglia, after injury the engrafted peripheral monocytes are resistant to depletion by colony stimulating factor 1 receptor (CSF1R) inhibitor and remain pro-inflammatory, expressing high levels of major histocompatibility complex II (MHC-II) for long-term. In the absence of ocular injury, on the other hand, the peripheral monocytes that repopulate the retina after CSF1R inhibition remain sensitive to CSF1R inhibition and can be re-depleted. The observed permanent neuroglia remodeling after injury constitutes a major immunological deviation that may contribute to progressive retinal degeneration. These findings may be relevant also to other degenerative conditions of the retina and central nervous system.

immunology↗

bioRxiv2018

Genotyping by sequencing of 393 Sorghum bicolor BTx623 x IS3620C recombinant inbred lines improves sensitivity and resolution of QTL detection

We describe a genetic map with a total of 381 bins of 616 genotyping by sequencing (GBS)-based SNP markers in a F6-F8 recombinant inbred line (RIL) population of 393 individuals derived from crossing S. bicolor BTx623 to S. bicolor IS3620C, a guinea line substantially diverged from BTx623. Five segregation distorted regions were found with four showing enrichment for S. bicolor alleles, suggesting possible selection during formation of this RIL population. A quantitative trait locus (QTL) study with this number of individuals, tripled relative to prior studies of this cross, provided resources, validated previous findings, and demonstrated improved power to detect plant height and flowering time related QTLs relative to other published studies. An unexpected low correlation between flowering time and plant height permitted us to separate QTLs for each trait and provide evidence against pleiotropy. Ten non-random syntenic regions conferring QTLs for the same trait suggest that those QTLs may represent alleles at genes functioning in the same manner since the 96 million year ago genome duplication that created these syntenic relationships, while syntenic regions conferring QTLs for different trait may suggest sub-functionalization after duplication. Collectively, this study provides resources for marker-assisted breeding, as well as a framework for fine mapping and subsequent cloning of major genes for important traits such as plant height and flowering time in sorghum.

genetics↗

bioRxiv2018

THEA: A novel approach to gene identification in phage genomes

MotivationCurrently there are no tools specifically designed for annotating genes in phages. Several tools are available that have been adapted to run on phage genomes, but due to their underlying design they are unable to capture the full complexity of phage genomes. Phages have adapted their genomes to be extremely compact, having adjacent genes that overlap, and genes completely inside of other longer genes. This non-delineated genome structure makes it difficult for gene prediction using the currently available gene annotators. Here we present THEA (The Algorithm), a novel method for gene calling specifically designed for phage genomes. While the compact nature of genes in phages is a problem for current gene annotators, we exploit this property by treating a phage genome as a network of paths: where open reading frames are favorable, and overlaps and gaps are less favorable, but still possible. We represent this network of connections as a weighted graph, and use graph theory to find the optimal path.\n\nResultsWe compare THEA to other gene callers by annotating a set of 2,133 complete phage genomes from GenBank, using THEA and the three most popular gene callers. We found that the four programs agree on 82% of the total predicted genes, with THEA predicting significantly more genes than the other three. We searched for these extra genes in both GenBanks non-redundant protein database and sequence read archive, and found that they are present at levels that suggest that these are functional protein coding genes.\n\nAvailability and ImplementationThe source code and all files can be found at: https://github.com/deprekate/THEA\n\nContactKatelyn McNair: deprekate@gmail.com

bioinformatics↗

bioRxiv2018

Agricultural Pollution Risks Influence Microbial Ecology in Honghu Lake

BackgroundAgricultural activities, such as stock-farming, planting industry, and fish aquaculture, can influence the physicochemistry and biology of freshwater lakes. However, the extent to which these agricultural activities, especially those that result in eutrophication and antibiotic pollution, effect water and sediment-associated microbial ecology, remains unclear.\n\nMethodsWe performed a geospatial analysis of water and sediment associated microbial community structure, as well as physicochemical parameters and antibiotic pollution, across 18 sites in Honghu lake, which range from impacted to less-impacted by agricultural pollution. Furthermore, the co-occurrence network of water and sediment were built and compared accorded to the agricultural activities.\n\nResultsPhysicochemical properties including TN, TP, NO3--N, and NO2--N were correlated with microbial compositional differences in water samples. Likewise, in sediment samples, Sed-OM and Sed-TN correlated with microbial diversity. Oxytetracycline and tetracycline concentration described the majority of the variance in taxonomic and predicted functional diversity between impacted and less-impacted sites in water and sediment samples, respectively. Finally, the structure of microbial co-associations was influenced by the eutrophication and antibiotic pollution.\n\nConclusionThese analyses of the composition and structure of water and sediment microbial communities in anthropologically-impacted lakes are imperative for effective environmental pollution monitoring. Likewise, the exploration of the associations between environmental variables (e.g. physicochemical properties, and antibiotics) and community structure is important in the assessment of lake water quality and its ability to sustain agriculture. These results show agricultural practices can negatively influence not only the physicochemical properties, but also the biodiversity of microbial communities associated with the Honghu lake ecosystem. And these results provide compelling evidence that the microbial community can be used as a sentinel of eutrophication and antibiotics pollution risk associated with agricultural activity; and that proper monitoring of this environment is vital to maintain a sustainable environment in Honghu lake.

microbiology↗

bioRxiv2017

WSL5, a pentatricopeptide repeat protein, is essential for chloroplast biogenesis in rice under cold stress

AbstactChloroplasts play an essential role in plant growth and development, and cold has a great effect on chloroplast development. Although many genes or regulators involved in chloroplast biogenesis and development have been isolated and characterized, identification of novel components associated with cold is still lacking. In this study, we reported the functional characterization of white stripe leaf 5 (wsl5) mutant in rice. The mutant developed white-striped leaves during early leaf development and was albinic when planted under cold stress. Genetic and molecular analysis revealed that WSL5 encodes a novel chloroplast-targeted pentatricopeptide repeat protein. RNA-seq analysis showed that expression of nuclear-encoded photosynthetic genes in the mutant was significantly repressed, and expression of many chloroplast-encoded genes was also significantly changed. Notably, the WSL5 mutation caused defects in editing of rpl2 and atpA, and in splicing of rpl2 and rps12. Chloroplast ribosome biogenesis was impaired under cold stress. We propose that WSL5 is required for normal chloroplast development in rice under cold stress.

genetics↗

bioRxiv2017

Boosting Gene Expression Clustering with System-Wide Biological Information: A Robust Autoencoder Approach

Gene expression analysis provides genome-wide insights into the transcriptional activity of a cell. One of the first computational steps in exploration and analysis of the gene expression data is clustering. With a number of standard clustering methods routinely used, most of the methods do not take prior biological information into account. In this paper, we propose a new approach for gene expression clustering analysis. The approach benefits from a new deep learning architecture, Robust Autoencoder, which provides a more accurate high-level representation of the feature sets, and from incorporating prior biological information into the clustering process. We tested our approach on two distinct gene expression datasets and compared the performance with two widely used clustering methods, hierarchical clustering and k-means, as well as with a recent deep learning clustering approach. As a result, our approach outperformed all other clustering methods on the labeled yeast gene expression dataset. Furthermore we showed that it is better in identifying the functionally common clusters than k-means on the unlabeled human gene expression dataset. The results demonstrate that our new deep learning architecture could generalize well the specific properties of gene expression profiles. Furthermore, the results confirm our hypothesis that the prior biological network knowledge could be helpful in the gene expression clustering task.

bioinformatics↗

bioRxiv2017

Mitochondrial genomes infer phylogenetic relationships among the oldest extant winged insects (Palaeoptera)

Phylogenetic relationships among the basal orders of winged insects remain unclear, in particular the relationship of the Ephemeroptera (mayflies) and the Odonata (dragonflies and damselflies) with the Neoptera. Insect evolution is thought to have followed rapid divergence in the distant past and phylogenetic reconstruction may therefore be susceptible to problems of taxon sampling, choice of outgroup, marker selection, and tree reconstruction method. Here we newly sequenced three mitochondrial genomes representing the two most diverse families of the Ephemeroptera, one of which is a basal lineage of the order. We then used an additional 90 insect mitochondrial genomes to reconstruct their phylogeny using Bayesian and maximum likelihood approaches. Bayesian analysis supported a basal Odonata hypothesis, with Ephemeroptera as sister group to the remaining insects. This was only supported when using an optimized data matrix from which rogue taxa and terminals affected by long-branch attraction were removed. None of our analyses supported a basal Ephemeroptera hypothesis or Ephemeroptera + Odonata as monophyletic clade sister to other insects (i.e., the Palaeoptera hypothesis). Our newly sequenced mitochondrial genomes of Baetis rutilocylindratus, Cloeon dipterum, and Habrophlebiodes zijinensis had a complete set of protein coding genes and a conserved orientation except for two inverted tRNAs in H. zijinensis. Increased mayfly sampling, removal of problematic taxa, and a Bayesian phylogenetic framework were needed to infer phylogenetic relationships within the three ancient insect lineages of Odonata, Ephemeroptera, and Neoptera. Pruning of rogue taxa improved the number of supported nodes in all phylogenetic trees. Our results add to previous evidence for the Odonata hypothesis and indicate that the phylogenetic resolution of the basal insects can be resolved with more data and sampling effort.

evolutionary biology↗

bioRxiv2017

Natural variation in stochastic photoreceptor specification and color preference in Drosophila

Each individual perceives the world in a unique way, but little is known about the genetic basis of variation in sensory perception. Here we investigated natural variation in the development and function of the color vision system of Drosophila. In the fly eye, the random mosaic of color-detecting R7 photoreceptor subtypes is determined by stochastic expression of the transcription factor Spineless (Ss). Individual R7s randomly choose between SsON or SsOFF fates at a ratio of 65:35, resulting in unique patterns but consistent proportions of cell types across genetically identical retinas. In a genome wide association study, we identified a naturally occurring insertion in a regulatory DNA element in the ss gene that lowers the ratio of SsON to SsOFF cells. This change in photoreceptor fates shifts the innate color preference of flies from green to blue. The genetic variant increases the binding affinity for Klumpfuss (Klu), a zinc finger transcriptional repressor that regulates ss expression. Klu is expressed at intermediate levels to determine the normal ratio of SsON to SsOFF cells. Thus, binding site affinity and transcription factor levels are finely tuned to regulate stochastic on/off gene expression, setting the ratio of alternative cell fates and ultimately determining color preference.

developmental biology↗

bioRxiv2017

Assembly Of Whole-Chromosome Pseudomolecules For Polyploid Plant Genomes Using Outcrossed Mapping Populations

The assembly of whole-chromosome pseudomolecules for plant genomes remains challenging due to polyploidy and high repeat content. We developed an approach for constructing complete pseudomolecules for polyploid species using genotyping-by-sequencing data from outcrossing mapping populations coupled with high coverage whole genome sequence data of a reference genome. Our approach combines de novo assembly with linkage mapping to arrange scaffolds into pseudomolecules. We show that the method is able to reconstruct simulated chromosomes for both diploid and tetraploid genomes. Comparisons to three existing genetic mapping tools show that our method outperforms the other methods in accuracy on both grouping and ordering, and is robust to the presence of substantial amounts of missing data and genotyping errors. We applied our method to three real datasets including a diploid Ipomoea trifida and two tetraploid potato mapping populations. The linkage maps show significant concordance with the reference chromosomes. We resolved seven assembly errors for the published Ipomoea trifida genome assembly as well as anchored an unplaced scaffold in the published potato genome.

bioinformatics↗

bioRxiv2017

Divergent In vitro MIC Characteristics and underlying isogenic mutations in host-specialized Pseudomonas aeruginosa

Clinical isolates of Pseudomonas aeruginosa (Pa) from patients with cystic fibrosis (CF) are known to differ from those associated with infections of non-CF hosts in colony morphology, drug susceptibility patterns, and genomic hypermutability. Although Pa isolates from CF have long been recognized for their overall higher resistance rate calculated generally by reduced \"percent susceptible\", this study takes the approach to compare and contrast Etest MIC distributions between two distinct cohorts of clinical strains (n=224 from 56 CF patients and n=130 from 68 non-CF patients respectively) isolated in 2013. Logarithmic transformed MIC (logMIC) values of 11 antimicrobial agents were compared between the two groups. CF isolates tended to produce heterogeneous and widely dispersed MICs compared to non-CF isolates. By applying a test for equality of variances, we were able to confirm that the MICs generated from CF isolates against 9 out of the 11 agents were significantly more dispersed than those from non-CF (p<0.02-<0.001). Quantile-quantiles plots indicated little agreement between the two cohorts of isolates. Based on whole genome sequencing of 19 representative CF Pa isolates, divergent gain- or loss-of-function mutations in efflux and porin genes and their regulators between isogenic or intra-clonal associates were evident. Not one, not a few, but the net effect all adaptive mutational changes in the genomes of CF Pa, both shared and unshared between isogenic strains, are responsible for the divergent heteroresistance patterns. Moreover, the isogenic variations are suggestive of a bacterial syntrophic lifestyle when \"lockedo inside a host focal airway environment over prolonged periods.\n\nSignificance statementBacterial heteroresistance is associated with niche specialized organisms interacting with host species for prolonged period of time, medically characterized by \"chronic focal infections\". A prime example is found in Pseudomonas aeruginosa isogenic/non-homogeneous isolates from patient airways with cystic fibrosis. The development of pseudomonal polarizing MICs in vitro to many actively used antimicrobial agents among isogenic isolates and \"Eagle-type\" heteroresistance patterns are common and characteristic. Widespread isogenic gene lesions were evident for defects in drug transporters, DNA mismatch repair, and many other structural or cellular functions--a result of pseudomonal symbiotic response to host selection. Co-isolation of extremely susceptible and resistant isogenic Pa strains suggests intra-airway evolution of a multicellular syntrophic bacterial lifestyle, which has laboratory interpretation and clinical treatment implications.

microbiology↗

bioRxiv2017

Identification and characterization of m6A circular RNA epitranscriptomes

This study brings together the expanding fields of RNA modifications and circular (circ) RNAs. We find that cells express thousands of m6A methylated circRNAs, with cell-type specificity observed between human embryonic stem cells and HeLa cells. m6A-circRNAs were identified by RNA sequencing of total RNA following ribosome depletion and m6A immunoprecipitation. The presence of m6A-circRNAs is corroborated by the identification of complexes between circRNAs and YTHDF1 and YTHDF2, proteins that \"read\" m6A sites in mRNAs.\n\nFurthermore, m6A modifications on non-linear RNAs depend on METTL3 and METTL14, the known m6A methyltransferase \"writer\" complex components, suggesting that circRNAs are methylated by the same complexes responsible for m6A modification of linear RNAs. Despite sharing m6A readers and writers, m6A-circRNAs are frequently derived from exons not methylated in mRNAs. Nevertheless, m6A-mRNAs that are methylated on the same exons as those composing m6A-circRNAs exhibit less stability than other m6A-mRNA, and this circRNA-mRNA cross-talk is regulated by YTHDF2. Thus, our results expand the m6A regulatory code through identification of the first circRNA epitranscriptome.

bioinformatics↗

bioRxiv2017

Ongoing human chromosome end extension driven by a primate ancestral genomic region revealed by analysis of BioNano genomics data

The majority of human chromosome ends remain incompletely assembled due to their highly repetitive structure. In this study, we use BioNano data to anchor and extend chromosome ends from two European trios as well as two unrelated Asian genomes. BioNano assembled chromosome ends are structurally divergent from the reference genome, including both missing sequence (10%) and extensions(22%). These extensions are heritable and in some cases divergent between Asian and European samples. Six ninths of the extension sequence in NA12878 can be confirmed and filled by nanopore data. We identify two sequence families in these sequences which have undergone substantial duplication in multiple primate lineages. We show that these sequence families have arisen from progenitor interstitial sequence on the ancestral primate chromosome 7. Comparison of chromosome end sequences from 15 species revealed that chromosome end missing sequence matches the corresponding phylogenetic relationship and revealed a rate of chromosome extension per chromosome of 0.0020 bp per year in average.

genomics↗