Biology subjects

Hong, Y.

Publications and source records attributed to Hong, Y..

7 recordsLinked to original sources

bioRxiv2018

Evolutionary rate covariation analysis of E-cadherin identifies Raskol as regulator of cell adhesion and actin dynamics in Drosophila

The adherens junction couples the actin cytoskeletons of neighboring cells to provide the foundation for multicellular organization. The core of the adherens junction is the cadherin-catenin complex that arose early in the evolution of multicellularity to link cortical actin to intercellular adhesions. Over time, evolutionary pressures have shaped the signaling and mechanical functions of the adherens junction to meet specific developmental and physiological demands. Evolutionary rate covariation (ERC) identifies genes with correlated fluctuations in evolutionary rate that can reflect shared selective pressures and functions. Here we use ERC to identify genes with evolutionary histories similar to shotgun (shg), which encodes the Drosophila E-cadherin (DE-Cad) ortholog. Core adherens junction components -catenin and p120-catenin displayed strong ERC correlations with shg, indicating that they evolved under similar selective pressures during evolution between Drosophila species. Further analysis of the shg ERC profile revealed a collection of genes not previously associated with shg function or cadherin-mediated adhesion. We then analyzed the function of a subset of ERC-identified candidate genes by RNAi during border cell (BC) migration and identified novel genes that function to regulate DE-Cad. Among these, we found that the gene CG42684, which encodes a putative GTPase activating protein (GAP), regulates BC migration and adhesion. We named CG42684 raskol (\"to split\" in Russian) and show that it regulates DE-Cad levels and actin protrusions in BCs. We propose that Raskol functions with DE-Cad to restrict Ras/Rho signaling and help guide BC migration. Our results demonstrate that a coordinated selective pressure has shaped the adherens junction and this can be leveraged to identify novel components of the complexes and signaling pathways that regulate cadherin-mediated adhesion.\n\nAuthor SummaryThe establishment of intercellular adhesions facilitated the genesis of multicellular organisms. The adherens junction, which links the actin cytoskeletons of neighboring cells, arose early in the evolution of multicellularity and selective pressures have shaped its function and molecular composition over time. In this study, we used evolutionary rate covariation (ERC) analysis to examine the evolutionary history of the adherens junction and to identify genes that coevolved with the adherens junction gene shotgun, which encodes the Drosophila E-cadherin (DE-Cad). ERC analysis of shotgun revealed a collection of genes with similar evolutionary histories. We then tested the role of these genes in border cell migration in the fly egg chamber, a process that requires the coordinated regulation of cell-cell adhesion and cell motility. Among these, we found that a previously uncharacterized gene CG42684, which encodes a putative GTPase activating protein (GAP), regulates the collective cell migration of border cells, stabilizes cell-cell adhesions and regulates the actin dynamics. Our results demonstrate that components of the adherens junction share an evolutionary history and that ERC analysis is a powerful method to identify novel components of cell adhesion complexes in Drosophila.

genetics↗

bioRxiv2018

Increased GITRL impairs the function of MDSCs and exacerbates primary Sjögren’s syndrome

It is largely unclear how MDSCs contribute to the development of primary Sjogrens syndrome (pSS). In experimental SS (ESS) mice, MDSCs were significantly increased but exhibited gradually diminished suppressive capacity during the disease progression. The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased with the development of pSS, and the increased GITRL was found to down-regulate the function of MDSCs while blocking GITR signal in MDSCs significantly restored their function and ameliorated ESS progression in mice. In pSS patients, expanded MDSCs expressed lower level of arginase were observed in patients with higher SSDAI. Moreover, the increased GITRL in serum was also found to closely correlate with the aberrant function of MDSCs. Together, our studies have demonstrated a critical role of GITRL in modulating the suppressive capacity of MDSCs in pSS, which may facilitate the validation of GITRL as a therapeutic target for the treatment of pSS.

immunology↗

bioRxiv2018

Comparative genomic analysis revealed rapid differentiation in the pathogenicity-related gene repertoires between Pyricularia oryzae and Pyricularia penniseti isolated from a Pennisetum grass

BackgroundsPyricularia is a multispecies complex that could infect and cause severe blast disease on diverse hosts, including rice, wheat and many other grasses. Although the genome size of this fungal complex is small [~40 Mbp for Pyricularia oryzae (syn. Magnaporthe oryzae), and ~45 Mbp for P. grisea], the genome plasticity allows the fungus to jump and adapt to new hosts. Therefore, deciphering the genome basis of individual species could facilitate the evolutionary and genetic study of this fungus. However, except for the P. oryzae subgroup, many other species isolated from diverse hosts, such as the Pennisetum grasses, remain largely uncovered genetically.\n\nResultsHere, we report the genome sequence of a pyriform-shaped fungal strain P. penniseti P1609 isolated from a Pennisetum grass (JUJUNCAO) using PacBio SMRT sequencing technology. We performed a phylogenomic analysis of 28 Magnaporthales species and 5 non-Magnaporthales species and addressed P1609 into a Pyricularia subclade that is distant from P. oryzae. Comparative genomic analysis revealed that the pathogenicity-related gene repertoires were fairly different between P1609 and the P. oryzae strain 70-15, including the cloned avirulence genes, other putative secreted proteins, as well as some other predicted Pathogen-Host Interaction (PHI) genes. Genomic sequence comparison also identified many genomic rearrangements.\n\nConclusionTaken together, our results suggested that the genomic sequence of the P. penniseti P1609 could be a useful resource for the genetic study of the Pennisetum-infecting Pyricularia species.

genomics↗

bioRxiv2018

U1 snRNP regulates chromatin retention of noncoding RNAs

Thousands of noncoding transcripts exist in mammalian genomes, and they preferentially localize to chromatin. Here, to identify cis-regulatory elements that control RNA-chromatin association, we developed a high-throughput method named RNA element for subcellular localization by sequencing (REL-seq). Coupling REL-seq with random mutagenesis (mutREL-seq), we discovered a key 7-nt U1 recognition motif in chromatin-enriched RNA elements. Reporter assays indicated a direct role for U1 snRNP recognition in regulating RNA-chromatin localization. Globally, U1 motifs and U1 binding are strongly enriched in long noncoding RNA (lncRNA) transcripts. Inhibition of U1 snRNA, and of U2 to a lesser degree, led to global reduction in chromatin association of hundreds of lncRNAs. For promoter- and enhancer-associated noncoding RNAs, U1 binds to their genomic neighborhoods, and their chromatin association depends on both U1 and U2 snRNAs. These findings reveal that U1 snRNP, perhaps together with the splicing machinery, acts widely to promote the chromatin association of noncoding transcripts.

molecular biology↗

bioRxiv2017

Prometheus: omics portals for interkingdom comparative genomic analyses

Functional analyses of genes are crucial for unveiling biological responses, for genetic engineering, and for developing new medicines. However, functional analyses have largely been restricted to model organisms, representing a major hurdle for functional studies and industrial applications. To resolve this, comparative genome analyses can be used to provide clues to gene functions as well as their evolutionary history. To this end, we present Prometheus (http://prometheus.kobic.re.kr),web-based omics portal that contains more than 17,215 sequences from prokaryotic and eukaryotic genomes. This portal supports interkingdom comparative analyses via a domain architecture-based gene identification system, Gene Search, and users can easily and rapidly identify single or entire gene sets in specific pathways. Bioinformatics tools for further analyses are provided in Prometheus or through BioExpress, a cloud-based bioinformatics analysis platform. Prometheus suggests a new paradigm for comparative analyses with large amounts of genomic information.

bioinformatics↗

bioRxiv2017

Mutational signatures of DNA mismatch repair deficiency in C. elegans and human cancers

1.Throughout their lifetime cells are subject to extrinsic and intrinsic mutational processes leaving behind characteristic signatures in the genome. One of these, DNA mismatch repair (MMR) deficiency leads to hypermutation and is found in different cancer types. While it is possible to associate mutational signatures extracted from human cancers with possible mutational processes the exact causation is often unknown. Here we use C. elegans genome sequencing of pms-2 and mlh-1 knockouts to reveal the mutational patterns linked to C. elegans MMR deficiency and their dependency on endogenous replication errors and errors caused by deletion of the polymerase {varepsilon} subunit pole-4. Signature extraction from 215 human colorectal and 289 gastric adenocarcinomas revealed three MMR-associated signatures one of which closely resembles the C. elegans MMR spectrum. A characteristic difference between human and worm MMR deficiency is the lack of elevated levels of NCG>NTG mutations in C. elegans, likely caused by the absence of cytosine (CpG) methylation in worms. The other two human MMR signatures may reflect the interaction between MMR deficiency and other mutagenic processes, but their exact cause remains unknown. In summary, combining information from genetically defined models and cancer samples allows for better aligning mutational signatures to causal mutagenic processes.

genomics↗

bioRxiv2017

Multiple reference genome sequences of hot pepper reveal the massive evolution of plant disease resistance genes by retroduplication

Transposable elements (TEs) provide major evolutionary forces leading to new genome structure and species diversification. However, the role of TEs in the expansion of disease resistance gene families has been unexplored in plants. Here, we report high-quality de novo genomes for two peppers (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum). Dynamic genome rearrangements involving translocations among chromosome 3, 5 and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs exhibited great abundance across the angiosperms, with most cases lineage-specific and thus recent events. Our study revealed that retroduplication has played key roles in the emergence of new disease-resistance genes in plants.

plant biology↗