Biology subjects

Ruan, H.

Publications and source records attributed to Ruan, H..

At least 19 recordsLinked to original sources

bioRxiv2026

A Phosphorylation-Induced Micellization switch in the low complexity domain of TDP-43

Abstract textPhase separation (PS) of the low-complexity domain (LCD) of TDP-43 is linked to pathogenic aggregates in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). Here, we show that extensive phosphorylation of the LCD C-terminus redirects its self-assembly. Coarse-grained Monte Carlo simulations predicted that 12 Ser phosphorylations partition the 148-residue LCD into a hydrophobic N-terminal and highly charged C-terminal block, favoring finite-sized micellization over macroscopic PS. In vitro, LCD phosphorylated by casein kinase 1 delta (CK1{delta}; mean of 12 phosphorylations by native mass spectrometry) and phosphomimetic 12D/12DD mutants formed spherical nanoparticles ({approx} 20-50 nm) above a low-micromolar critical micelle concentration, whereas the unphosphorylated LCD underwent reversible PS that matured into fibrils. Increasing ionic strength shifted the mutants toward anisotropic morphologies (worm-like 12D micelles and rigid 12DD nanocylinders). Turbidity assays and confocal imaging directly visualized the absence of PS in the phosphorylated form. Negative-stain and cryo-EM confirmed the spherical micellar architecture for the phosphorylated LCD and 12D/12DD mimics. Our data identify phosphorylation as a molecular switch tuning macrophase separation and fibril formation of TDP-43 LCD, providing a framework for an aggregation-protective role through microphase separation into size-limited micelles. Whether these assemblies are stable or kinetically trapped on pathological timescales remains unclear.

biophysics↗

bioRxiv2026

Disrupted Higher-Order Topology in OCD Brain Networks Revealed by Hodge Laplacian - an ENIGMA Study

Brain disorders are increasingly understood as disorders of distributed brain circuits, yet functional connectivity (FC), the dominant framework for mapping them, treats the brain as a collection of pairwise relationships between regions and cannot represent pathology distributed across coordinated sets of connections. We introduce a Hodge-Laplacian topological framework that localizes higher-order "loop" (1-cycle) organization within functional connectome, maps each loop to specific edges and networks, and yields a subject-level measure of loop expression. Applied to resting-state fMRI from the ENIGMA-OCD consortium (1,024 patients and 1,028 controls across 28 sites), the framework identified 93 loop-level abnormalities in obsessive-compulsive disorder (OCD), concentrated in frontoparietal and somatomotor systems. The edges forming these loops largely showed no significant differences between groups, indicating that the abnormalities were invisible to conventional FC analysis. The frontoparietal and somatomotor loop clusters recurred across the clinical subgroups, suggesting convergence on a shared higher-order phenotype. Robustness analyses showed the loop signal reflected higher-order organization rather than an artifact of individual edges, the network backbone, or any single site. These results indicate that coordinated, multi-edge pathology exists and can be localized even when pairwise analyses fail to detect it, positioning higher-order topology as a generalizable axis for mapping circuit pathology across psychiatric and neurological disorders.

neuroscience↗

bioRxiv2025

Efficient Generation of Humanized Cloned Cattle via Embryonic Stem Cell-Mediated Dual-Round Site-Specific Editing

Transgenic cloning allows genetic modification in cattle, yet its translational potential is constrained by low cloning efficiency and limited gene-editing capacity, due largely to the restricted proliferative ability of somatic donor cells. Pluripotent stem cells (PSCs), with their unlimited self-renewal ability, represent a promising alternative to overcome these bottlenecks. Here, we first established stable bovine epiblast stem cell lines (bEpiSCs) and achieved site-specific integration of the HCSN2-HLF-GFP cassette into the {beta}-casein locus, with high transfection (72.07%) and correct integration efficiency (80.48%). Following Cre LoxP mediated excision of the selectable marker, we obtained marker free HCSN2-HLF bEpiSCs that retained pluripotency markers, tri lineage differentiation potential, and supported target protein expression in immortalized bovine mammary epithelial cells. When used as nuclear donors, these cells produced blastocysts with quality comparable to in vitro fertilization (IVF) embryos. Notably, cloning with HCSN2-HLF bEpiSCs resulted in the birth of twelve calves, with significantly higher birth and survival rates (30.71% and 16.74%, respectively) than those obtained using fibroblasts. Both PCR-based genotyping of the edited loci and microsatellite kinship analysis confirmed that all cloned calves were genetically derived from the HCSN2-HLF bEpiSCs. Collectively, this study establishes an efficient embryonic stem cell based platform for targeted gene editing and rapid production of multigene edited cloned cattle, offering a scalable strategy with strong potential for industrial translation.

bioengineering↗

bioRxiv2025

O-GlcNAcylation and an importin-β radial gradient keep the FG barrier liquid in live-cell nuclear pores

Summary ParagraphThe nuclear pore complex (NPC) regulates the molecular traffic between nucleus and cytoplasm.1,2 Its permeability barrier is formed by intrinsically disordered proteins (IDPs) known as FG-nucleoporins (FG-NUPs), whose physical state has long been debated.3-13 Deciphering how FG-NUPs behave inside living cells is crucial for understanding how the NPC achieves selective and rapid transport. Here, by combining site-specific labelling with picosecond time-resolved fluorescence anisotropy, we reveal that FG domains exhibit nanosecond-scale, liquid-like mobility in live cells, yet undergo a liquid-to-solid transition in vitro. Experiments and coarse-grained molecular dynamics simulations further show that importin-{beta}, a major nuclear transport receptor, and O-linked {beta}-N-acetylglucosamine (O-GlcNAc), a key post-translational modification of FG-NUPs together stabilise the dynamic FG network. Finely balanced FG-FG interactions modulated by O-GlcNAcylation, along with FG-importin-{beta} interactions, maintain liquidity and enrich importin-{beta} near the NPC periphery, while extended FG domains remain in the central channel to form the transport barrier. These findings reconcile conflicting models of FG-NUP organisation4,6,8,10,14,15 and explain the recent observations in high-resolution MINFLUX studies of importin-{beta} depletion from the pore centre in mammalian cells.16 Beyond resolving debates over FG-NUP behaviour, our study underscores the importance of studying IDPs in their cellular context, with broader implications for understanding IDP-related diseases, including viral infections, cancer, and neurodegenerative disorders.

biophysics↗

bioRxiv2025

Adaptive Feature-Weighted Stacking Ensemble for Short-Term Risk Prediction of Prolonged Length of Stay in Elderly Trauma Patients

The Adaptive Feature-Weighted Stacking Ensemble (AFWSE) model is presented here as a new machine learning method that provides staged prediction of prolonged length of stay in trauma patients. We used a retrospective dataset of elderly trauma patients using simulated data from publicly available feature characteristics. AFWSE is designed to combine different base learners like logistic regression, random forest, and gradient boosting, into a stacked ensemble with an adaptive feature weighting mechanism that allows researchers to identify complex patterns while emphasizing clinically relevant features. The AFWSE model was compared to standard machine learning methods, specifically, logistic regression, random forest, gradient boosting, and neural networks, demonstrating consistently better predictive validity and accuracy. The AFWSE identified important features which included older age, injury site, injury mechanism, or type of trauma, and Glasgow Coma Scale, which contributes to the existing body of clinical evidence. The AFWSE model mechanism and its potential clinical interpretation and implications are discussed, along with addressing the recognized limitations of using simulated datasets.

bioengineering↗

bioRxiv2025

BIN1 deficiency leads to DNA damage and neuronal insulin resistance through ATM dysregulation

The major neuronal isoform of the AD risk gene BIN1 is specifically reduced in patients. In the present work, we demonstrate that BIN1 is necessary for intact insulin signaling and its loss leads to cellular-level insulin resistance. Persistently activated mTORC1 feedback inhibits the insulin signaling; meanwhile, ATM-dependent DNA Damage Response decreases the expression of multiple insulin signaling pathway members. Unexpectedly, nuclear ATM activation is accompanied by autophagic degradation of the cytoplasmic ATM, rendering neurons susceptible to oxidative stress, which predisposes oxidative DNA damage, DNA strand breaks, and ATM-dependent DNA Damage Response. Treating BIN1-deficient mice with rapamycin or liraglutide to improve the insulin response, or with the natural antioxidant alpha-lipoic acid to attenuate oxidative stress, both effectively preserved the spatial cognitive ability. Lastly, we reanalyzed a single-cell transcriptomic dataset from human neurons and identified positive correlations between levels of BIN1 and the insulin signaling, as well as neuronal activity. Together, this work revealed an ATM-centered mechanism that globally damages neuronal health in BIN1-deficient pyramidal neurons, which could be a driving force in the AD disease course.

cell biology↗

bioRxiv2025

Differential conformational expansion of Nup98-HOXA9 oncoprotein in micro- and macrophases

Transcription factors (TFs) play a central role in gene regulation by binding to specific DNA sequences and orchestrating the transcriptional machinery. A majority of eukaryotic TFs have a block copolymer architecture, with at least one block being a folded DNA interaction domain, and another block being highly enriched in intrinsic disorder. Multivalent interactions in the intrinsically disordered region (IDR) can contribute to phase separation into macroscopic condensates. In this study, we focus on Nup98-HOXA9 (NHA9), a chimeric transcription factor implicated in leukemogenesis, in which two FG-repeat-rich IDRs derived from Nup98 get fused to the C-terminal part of transcription factor HOXA9. By integrating experiments and simulations, we examined the structural dynamics of NHA9s FG domain across assembly states. We found that the FG domain has different conformational compactness in the monomeric state, oligomeric, and densely packed condensate state. Notably, the oligomeric state exhibits micelle-like organisation, with the DNA-binding domain exposed at the periphery. While their architecture is non-random, their sizes depend on NHA9 concentration, consistent with non-core-shell spherical micelles. Molecular dynamics simulations support the expansion behaviour of NHA9s FG domain as oligomeric assemblies grow in size and reveal micelle-like structural features in oligomeric assemblies. These findings offer molecular insight into the phase behaviour of NHA9 and highlight the dynamic conformational transitions of IDRs during condensate formation, with implications for understanding transcriptional regulation in cancer.

biophysics↗

bioRxiv2025

Sky islands of Southwest China. II: Unraveling hidden species diversity of talpid moles using phylogenomics and skull-based deep learning

The sky islands of Southwest China, characterized by dramatic topographical and climatic variations, are prominent hotspots of biodiversity and endemism. Organisms inhabiting middle-to-high elevation habitats in this region are geographically isolated within distinct mountain chains, which over geological time have been subjected to isolation-by-distance and isolation-by-environment. These processes have led to profound allopatric diversification and strong phylogeographic structuring, resulting in a plethora of genetically distinct cryptic species, as is becoming increasingly evident for many small mammal families. However, morphological conservatism can pose significant challenges in delineating these clades within species complexes. In this study, we leverage artificial intelligence technologies to unravel the hidden species diversity of moles (family Talpidae) in Southwest Chinas sky islands. We first employed ultraconserved elements (UCEs) to investigate the evolutionary history of talpid moles, conducted molecular species delimitation using mitochondrial and multi-locus genes, and utilized both traditional and geometric morphometrics to examine their morphological disparity. To address the challenges of morphology based cryptic species identification, we developed a deep learning Hierarchical Identification of Species NETwork (HIS-NET) to create an image-based model that analyzes four different views of the skull/mandible to distinguish genera and species hierarchically. HIS-NET not only achieved expert-level accuracy in species identification but also effectively distinguished between cryptic and known species, aiding in the identification of key morphological variation intervals. Our results support the recognition of allopatrically distributed taxa in Euroscaptor and Parascaptor as full species, thereby confirming that species diversity in this region remains underestimated. Beyond advancing our understanding of speciation in this unique and fragile ecosystem, our study serves as a proof-of-concept, demonstrating the power of deep learning in unraveling hidden biodiversity within this and other species complexes.

zoology↗

bioRxiv2023

USP48/USP31 Is a Nuclear Deubiquitinase that Potently Regulates Synapse Remodeling

Deubiquitinases present locally at synapses regulate synaptic development, function, and plasticity. It remains largely unknown, however, whether deubiquitinases localized outside of the synapse control synapse remodeling. Here we identify ubiquitin specific protease 48 (USP48; formerly USP31) as a nuclear deubiquitinase mediating robust synapse removal. USP48 is expressed primarily during the first postnatal week in the rodent brain and is virtually restricted to nuclei, mediated by a conserved, 13-amino acid nuclear localization signal. When exogenously expressed, USP48, in a deubiquitinase and nuclear localization-dependent manner, induces striking filopodia elaboration, marked spine loss, and significantly reduced synaptic protein clustering in vitro, and erases [~]70% of functional synapses in vivo. USP48 interacts with the transcription factor NF-{kappa}B, deubiquitinates NF-{kappa}B subunit p65 and promotes its stability and activation, and up-regulates NF-{kappa}B target genes known to inhibit synaptogenesis. Depleting NF-{kappa}B prevents USP48-dependent spine pruning. These findings identify a novel nucleus-enriched deubiquitinase that plays critical roles in synapse remodeling.

neuroscience↗

bioRxiv2023

Ulinastatin Ameliorates Cardiac Ischemia/Reperfusion Injury via Inhibiting the tissue kallikrein-kinin system

BackgroundEndothelial cells (ECs) are considered more sensitive to cardiac ischemia/reperfusion (I/R) injury compared to cardiomyocytes. However, current research is mainly focused on molecular mechanisms and preventive strategies targeting cardiomyocyte I/R injury, whereas insufficient attention is placed on protecting endothelial function. Methods and ResultsIn this study, we established an interlink among ulinastatin (UIT; a serine protease inhibitor), the kallikrein-kinin system (KKS), and EC injury in response to cardiac reperfusion for the first time, using in vitro and in vivo experiments, and bioinformatic analysis. Our data indicated that UTI affected I/R by inhibiting the activation of KKS and simultaneously down-regulating both bradykinin receptor 1 (Bdkrb1) and bradykinin receptor 2 (Bdkrb2) related signaling such as extracellularsignal-regulated kinase (ERK)/inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS), thereby reducing infarct size, attenuating inflammation and edema, and improving cardiac function and mortality. Interestingly, UIT significantly suppressed KLK1 activity but did not down-regulate the KKS in normal conditions, suggesting inhibition of KLK1 might be the crucial mechanism for UIT-induced cardioprotection in reperfusion injury. Moreover, knockdown of Bdkrb1 in reperfusion-induced cardiac endothelial cells (MCECs) injury significantly prevented ERK translocation into the nucleus, reducing apoptosis, junction disruption, and expression levels of cytokines, whereas Bdkrb2 deletion could not protect MCECs against I/R injury. ConclusionsOur findings imply that inhibition of KLK1/Bdkrb1 is a critical target for UIT in the treatment of reperfusion-induced cardiac endothelial inflammation, apoptosis, and leakage and might be a potential therapeutic strategy for cardiac reperfusion injury.

cell biology↗

bioRxiv2023

Cholecystokinin-A Signaling Regulates Automaticity of Pacemaker Cardiomyocytes and Shortens Sinus Node Recovery Time

AimsThe behavior of pacemaker cardiomyocytes (PCs) in the sinoatrial node (SAN) is modulated by neurohormonal and paracrine factors, many of which signal through G-protein coupled receptors (GPCRs). The aims of the present study are to catalog GPCRs that are differentially expressed in the mammalian SAN and to define the acute physiological consequences of activating the cholecystokinin-A signaling system in isolated PCs. Methods and ResultsUsing bulk and single cell RNA sequencing datasets, we identify a set of GPCRs that are differentially expressed between SAN and right atrial tissue, including several whose roles in PCs and in the SAN have not been thoroughly characterized. Focusing on one such GPCR, Cholecystokinin-A receptor (CCKAR), we demonstrate expression of Cckar mRNA specifically in mouse PCs, and further demonstrate that subsets of SAN fibroblasts and neurons within the cardiac intrinsic nervous system express cholecystokinin, the ligand for CCKAR. Using mouse models, we find that while baseline SAN function is not dramatically affected by loss of CCKAR, the firing rate of individual PCs is slowed by exposure to sulfated cholecystokinin-8 (sCCK-8), the high affinity ligand for CCKAR. The effect of sCCK-8 on firing rate is mediated by reduction in the rate of spontaneous phase 4 depolarization of PCs and is mitigated by activation of beta-adrenergic signaling. Conclusions(1) PCs express many GPCRs whose specific roles in SAN function have not been characterized, (2) Activation of the the cholecystokinin-A signaling pathway regulates PC automaticity.

physiology↗

bioRxiv2020

Aging-vulnerable and -resilient trajectories of specific motor circuit function in oxidation- and temperature-stressed Drosophila

We examined several sensory-motor processing circuits in Drosophila across the lifespan and uncovered distinctive age-resilient and age-vulnerable trajectories in their established functional properties. We observed relatively little deterioration toward the end of lifespan in the giant-fiber (GF) and downstream circuit elements responsible for the jump-and-flight escape reflex. In contrast, we found substantial age-dependent modifications in the performance of GF inputs and other circuits driving flight motoneuron activities. Importantly, in high temperature (HT)-reared flies (29 {degrees}C), the characteristic age-dependent progression of these properties was largely maintained, albeit over a compressed time scale, lending support for the common practice of expediting Drosophila aging studies by HT rearing. We discovered shortened lifespans in Cu2+/Zn2+ Superoxide Dismutase 1 (Sod) mutant flies were accompanied by alterations distinct from HT-reared flies, highlighting differential effects of oxidative vs temperature stressors. This work also establishes several age-vulnerable parameters that may serve as quantitative neurophysiological landmarks for aging in Drosophila.

neuroscience↗

bioRxiv2020

The Relationship Between Motor Fitness, Fundamental Movement Skills, and Functional Movement Screen in Primary School Children

This study investigates motor fitness (MF), fundamental movement skills (FMS), and functional movement screen (FMS) in 7-10-year-old children, and evaluates the relationship between FMS , MF and FMS combination with Seefeldts model for empirical research, thus to present effective strategies of physical development in children. A class was randomly selected in four school grades (1-4) along with 30 students from each to take the Test of Gross Motor Development-2 (TGMD-2). A total of 117 children (42 girls, aged 7-10) participated in three tests: TGMD-2, MF tests, and FMS. MF levels (good, fair, and poor) and FMS levels (high, moderate, and low) were classified according to specific percentile ranges. A multiple (RxC) chi-square test analysis of the relationship between MF, FMS, and FMS was applied and post hoc testing estimated the possibility of FMS and FMS predicting MF. The results showed that only 43% of children were rated "good" on MF. Most fourth-grade students exhibited a certain gap with mature FMS (TGMD-2 score 70.13{+/-}9.68< 96 full scores). Boys scored significantly higher on the object control subtest and the TGMD-2 total score compared to girls (p<0.001), while girls had a significantly greater score than boys on the FMS (p=0.001). The results of multiple chi-square demonstrated FMS to be weakly correlated with MF, {chi}2 (4,N=117) =14.605, p =0.006< 0.01, Cramers V = 0.25. Both 60.5% of "excellent" FMS and 59.6% of "high" FMS children were categorized as having a "good" MF level. On the other hand, only 23.1% of the "worst" FMS and 24.3% of "low" FMS individuals were classified as having a "good" MF level. Our results suggest that MF, FMS, FMS are relatively independent systems linking with each other, generating mutual interaction in childrens motor development. At different stages or different advantages of them motor development, we may emphasize training one or a few parts.

scientific communication and education↗

bioRxiv2020

CRISPR-Cas9 integrates exogeneous sorting new recombinant DNA in the model tree Populus trichocarpa

CRISPR-mediated genome editing has become a powerful tool for genetic modification of biological traits. However, developing an efficient, site-specific, gene knock-in system based on homology-directed DNA repair (HDR) remains a significant challenge in plants, especially in woody species like poplar. Here, we show that simultaneous inhibition of non-homologous end joining (NHEJ) recombination cofactor XRCC4 and overexpression of HDR enhancer factors CtIP and MRE11 can improve the HDR efficiency for gene knock-in. Using this approach, the BleoR gene was integrated onto the 3' end of the MKK2 MAP Kinase gene to generate a BleoR-MKK2 fusion protein. Based on exogenous BleoR expression, the HDR-mediated knock-in efficiency was up to [~]40-fold greater when using a XRCC4 silencing incorporated with a combination of CtIP and MRE11 overexpression compared to no HDR enhancement or NHEJ silencing. Furthermore, this corporation of HDR enhancer overexpression and NHEJ repression also resulted in 7-fold fewer CRISPR-induced Insertions and Deletions (InDels), resulting in no functional effects on MKK2-based salt stress responses in poplar. Therefore, this approach may be useful not only in poplar and plants or crops but also in mammalians for improving CRISPR-mediated gene knock-in efficiency.

plant biology↗

bioRxiv2020

Response patterns and mechanisms of plants to water stress

Plants are key to the functionality of many ecosystem processes. The duration and intensity of water stress are anticipated to increase in the future; however, an elucidation of the responses of plants to water stress remains incomplete. For this study, we present a global meta-analysis derived from 1301 paired observations from 84 studies to evaluate the response patterns and mechanisms of plants to water stress. The results revealed that while water stress inhibited plant growth and photosynthesis, reactive oxygen species (ROS), plasma membrane permeability, enzymatic antioxidants, and non-enzymatic antioxidants increased. These responses generally increased with the intensity of water stress but were mitigated with experimental duration. Our findings suggested that the overproduction of ROS was the primary mechanism of plants in response to water stress and that plants tend to acclimate to water stress over time to some extent. Our synthesis provides a framework for understanding the responses and mechanisms of plants under drought conditions. One senence summaryThe overproduction of ROS was the primary mechanism of plants in response to water stress and that plants tend to acclimate to water stress over time to some extent.

plant biology↗

bioRxiv2020

Inactivation of LCN2/EGR1 Promotes Oligodendrocyte Progenitor Cell Differentiation and Remyelination after White Matter Injury

The insufficient remyelination due to the impaired oligodendrocyte precursor cell differentiation and maturation is highly associated with irreversible white matter injury and neurological deficits. Consequently, inhibitory components and microenvironment for remyelination might serve as potential therapeutic targets for treating white matter injury after acute central nervous system injury and neurodegeneration diseases. Lipocalin-2 was recently reported to corelate with white matter in both atypical, acute white matter injured disease subarachnoid hemorrhage and typical, chronic white matter injured disease multiple sclerosis. To elucidate the role and underlying mechanism of Lipocalin-2 in oligodendrocyte precursor cell differentiation and remyelination, we used genetic inhibition and a constitutive conditional knockout model with subarachnoid hemorrhage or multiple sclerosis. We found that the genetic inhibition of the increase in Lipocalin-2 promoted oligodendrocyte precursor cell differentiation, remyelination, and functional recovery after subarachnoid hemorrhage or multiple sclerosis. Unexpectedly, the inhibition of Lipocalin-2 did not reduce glial activation and inflammation. Lipocalin-2 was shown to activate Early Growth Response Protein 1 in oligodendrocyte precursor cells, which is partly regulated by its receptor SLC22A17. In the conditional knockout of Early Growth Response Protein 1 in oligodendrocyte precursor cells, we discovered enhanced oligodendrocyte precursor cell differentiation in developing and injured white matter; consistently, the specific inactivation of Early Growth Response Protein 1 promoted remyelination and neurological recovery after subarachnoid hemorrhage or multiple sclerosis. Thus, we propose that following white matter injury in humans, the increase in Lipocalin-2 activates Early Growth Response Protein 1 and consequently impair oligodendrocyte precursor cell differentiation and myelin repair. Our results suggest that therapies specifically inactivating Lipocalin-2/ Early Growth Response Protein 1 signal in oligodendroglial lineage cells could represent a novel strategy to enhance differentiation and remyelination in white matter injury patients.

neuroscience↗

bioRxiv2018

Exploration of miRNA-mediated fertility regulation network of cytoplasmic male sterility during flower bud development in soybean

Cytoplasmic male sterility (CMS) plays an important role in the production of soybean hybrid seeds. MicroRNAs (miRNAs) are a class of non-coding endogenous ~21 nt small RNAs that play crucial roles in flower and pollen development by targeting genes in plants. Here, two small RNA libraries and two degradome libraries were constructed from the flower buds of the soybean CMS line NJCMS1A and its restorer (Rf) line NJCMS1C. Following high-throughput sequencing, 558 known miRNAs, 103 novel miRNAs on the other arm of known pre-miRNAs, 10 novel miRNAs, and a number of base-edited miRNAs were identified. Among the identified miRNAs, 76 differentially expressed miRNAs were discovered with greater than two-fold changes between NJCMS1A and NJCMS1C. By degradome analysis, a total of 466 distinct transcripts targeted by 200 miRNAs and 122 distinct transcripts targeted by 307 base-edited miRNAs were detected. Further integrated analysis of transcriptome and small RNA found some miRNAs and their targets expression patterns showing a negative correlation, such as miR156b-GmSPL and miR4413b-GmPPR. Previous reports showed that these targets might be related to flower bud development, suggesting that miRNAs might act as regulators of soybean CMS fertility. These findings may provide a better understanding of the miRNA-mediated regulatory networks in CMS mechanisms of soybean.

genomics↗

bioRxiv2018

The effector of Hippo signaling, Taz, is required for formation of the micropyle and fertilization in zebrafish

The mechanisms that ensure fertilization of eggs by a single sperm are not fully understood. In all teleosts, a channel called the micropyle is the only route of entry for sperm to enter and fertilize the egg. The micropyle forms by penetration of the developing vitelline envelope by a single specialized follicle cell, the micropylar cell, which subsequently degenerates. The mechanisms underlying micropylar cell specification and micropyle formation are poorly understood. Here, we show that an effector of the Hippo signaling pathway, the Transcriptional co-activator with a PDZ-binding domain (Taz), plays crucial roles in micropyle formation and fertilization in zebrafish. Genome editing mutants affecting taz can grow to adults, however, eggs from homozygous taz females are not fertilized even though oocytes in mutant females are histologically normal with intact animal-vegetal polarity, complete meiosis and proper ovulation. However, taz mutant eggs have no micropyle. We show that Taz protein is specifically enriched from mid-oogenesis onwards in two follicle cells located at the animal pole of the oocyte, and co-localizes with the actin and tubulin cytoskeleton. Taz protein and micropylar cell are not detected in taz mutant ovaries. Our work identifies a novel role for the Hippo/Taz pathway in micropylar cell specification in zebrafish, and uncovers the molecular basis of micropyle formation in teleosts.

developmental biology↗