Biology subjects

Wang, H.-J.

Publications and source records attributed to Wang, H.-J..

5 recordsLinked to original sources

bioRxiv2026

Structure and energy transfer of a minimal PSI-LHCI supercomplex with FNR binding from a terrestrial eustigmatophyte

Soil microalgae endure harsh terrestrial stressors, such as intense light. Eustigmatophytes are an independent evolutionary branch within stramenopiles and occupy diverse aquatic and terrestrial environments, but the structural organization of their photosynthetic apparatus remains poorly understood. Here, we determined the cryo-electron microscopy structure of a photosystem I-light-harvesting complex I (PSI-LHCI) supercomplex bound with ferredoxin-NADP+ oxidoreductase (FNR) from the terrestrial eustigmatophyte Vischeria stellata at 2.44 [A] resolution. The supercomplex contains a monomeric PSI core associated with only three LHCI subunits, representing the smallest PSI-LHCI reported among structurally characterized red-lineage PSI complexes composed of violaxanthin-Chl a proteins (VCPs). The three VCPIs with distinct structure features and arrangements form a compact belt along the PsaL-PsaI-PsaM side of PSI. The structure also resolves a 43-residue N-terminal segment of FNR (FNR-N) bound to the PSI stromal surface, which is stabilized by both a eustigmatophyte-conserved insertion in PsaL and the N-terminal region of PsaD. In contrast, the catalytic region of FNR was not resolved, suggesting conformational flexibility. Computational simulations indicate potential excitation-energy-transfer pathways connecting the three VCPI subunits to the PSI core and highlight lineage-specific pigments that maintain energetic connectivity within the exceptionally compact antenna. Our analysis further reveals conservation of FNR tethering despite pronounced diversification of antenna size and organization. These findings uncover a modular evolutionary principle in which PSI acceptor-side organization is retained while the light-harvesting antenna is extensively remodeled, providing a framework for understanding the diversification of photosynthetic energy conversion across ecological transitions.

plant biology↗

bioRxiv2026

SMS: Symmetric Mediation Statistics for Powerful High-Dimensional Mediation Analysis

BackgroundMediation analysis of high-dimensional features, particularly molecular-level omics features, provides important opportunities to uncover biological mechanisms underlying human health and disease. However, two central statistical challenges remain: testing the composite-null hypothesis and maintaining power when the exposure-mediator and mediator-outcome associations differ substantially in statistical significance. Existing methods typically rely on accurate estimation of the proportions of the three null types or on the maximum of the two association p-values, and may not always control the FDR well and may have limited power under imbalanced significance. MethodsWe propose SMS, a new statistical framework based on symmetric mediation statistics. By exploiting symmetry, SMS calibrates the composite null distribution as a whole for FDR control. It also allows flexible combinations of the two association p-values, including the maximum, and then enables construction of an omnibus test. Moreover, it permits direct use of effect-size estimates, bypassing the need to compute p-values. ResultsSMS controlled the FDR across a wide range of simulation scenarios while achieving a substantial sensitivity gain, often around 20 percentage points, over existing methods including HDMT, DACT, and DEI-B. Applications to a metabolomics dataset and a DNA methylation dataset further corroborated these findings. Notably, SMS discovered five plausible mediators in the metabolomics dataset that were missed by all existing methods considered.

bioinformatics↗

bioRxiv2024

Recruitment of SH3P2-DRP1A by HYCCIN2 Drives Membrane Tubulation in Arabidopsis Embryonic Cell Plate Formation

Cytokinesis marks the culmination of cell division when the cytoplasm undergoes division to yield two daughter cells. This intricate process encompasses various biological phenomena, including the organization of the cytoskeleton and the dynamics of vesicles. The development of the cell plate aligns with alterations in the cytoskeleton structure and vesicles derived from the trans-Golgi, ultimately resulting in the formation of the planar cell plate. Nevertheless, the coordination of these processes in plants remains to be determined. Here, we introduce HYCCIN-CONTAINING2 (HYC2) as a pivotal cytoskeleton cross-linking protein that accumulates at phragmoplasts and plays a crucial role in cell plate formation. A genetic study involving the depletion of HYC2 post-anaphase in Arabidopsis revealed HYC2s function in cell plate formation. HYC2 interacted with dynamin-related protein 1A (DRP1A) and SH3 domain-containing protein 2 (SH3P2), essential for membrane tubulation during cell plate formation. The recruitment of SH3P2 and DRP1A to the cell plate and phragmoplast organization was compromised in homozygous hyc2-2 mutant globular embryos. Our results shed light on the cytoskeletal function of HYC2 in assembling the cell plate, potentially by guiding vesicles containing SH3P2-DRP1A to the planar cell plate. Significance statementDuring plant cell division, a new membrane is constructed at the division plane, and vesicles fuse to form a transient compartment known as the cell plate. This structure undergoes stabilization via membrane remodeling events, including tubulation, to generate robust membrane intermediates. Apart from DRP1A and SH3P2, our understanding of other protein components involved in membrane remodeling still needs to be completed. HYC2 is a plant counterpart to the human Hyccin protein involved in neuronal myelination and displaying bundling capabilities for microtubules and microfilaments. Our study demonstrates that HYC2 is crucial in recruiting proteins during membrane tubulation in the cell plate formation in developing Arabidopsis embryos. These findings underscore the molecular function and vital role of the Hyccin protein in cell plate formation. One Sentence SummaryPlant HYC2 displays bundling capabilities for microtubules and microfilaments to recruit DRP1A and SH3P2 during membrane tubulation in the cell plate formation in developing Arabidopsis embryos.

plant biology↗

bioRxiv2023

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study, we dissected the roles of BMP receptor 1a (Bmpr1a)- mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

developmental biology↗

bioRxiv2021

Copy number variation profile-based genomic subtyping of premenstrual dysphoric disorder in Chinese

Premenstrual dysphoric disorder (PMDD) affects nearly 5% women of reproductive age. The symptomatic heterogeneity, along with largely unknown genetics, of PMDD have greatly hindered its effective treatment. In the present study, 127 Chinese PMDD patients of the invasion and depression subtypes clinically differentiated by us earlier were analyzed together with 108 non-PMDD controls for genome-wide copy number variations (CNVs). Germline genomic DNA samples from white blood cells were subjected to AluScan sequencing-based CNV profiling, which enabled clustering of patient samples readily into the V and D groups, dominated by the "invasion" and "depression" clinical subtypes, respectively; the CNVs obtained with 100-kb windows yielded two clusters that were correlated with these subtypes with a consistency of up to 89.8%. Diagnostic correlation- and frequency-based CNV features of either CNV-gain (CNVG) or CNV-loss (CNVL) that could differentiate between V and D subtypes were selected and analyzed. CNVG features located preferentially in S2-phase replicating regions and enriched with steroid hormone biosynthesis pathway of genes were found protective against PMDD. Moreover, machine learning employing the correlation-based CNV features could predict with >80% accuracy whether a genomic sample was D-type, V-type or control. In terms of their CNV profiles, the D- and V-types differed more from one another than from the controls, thereby providing a genomic basis for the clinical D-V subtyping of PMDD. Genome-wide profiling of CNVs, as a new approach to complex disease genetics, has revealed recurrent CNVs and genomic features beyond individual genes and mutations underlying PMDD clinical diversity.

genomics↗