Biomedical subjects

Yunhai Li

Publications and source records attributed to Yunhai Li.

6 recordsLinked to original sources

PubMed2026

Primate-specific regulation of the human glycosphingolipid gatekeeper UGCG.

Glycosphingolipids are essential membrane components that organize lipid microdomains and orchestrate cellular signalling, differentiation and neuronal function1-4. In humans, these functions arise from a repertoire of several hundred glycosphingolipid species generated through stepwise glycan elaboration5,6. Entry into this network is controlled by a single committed reaction catalysed by UDP-glucose ceramide glucosyltransferase (UGCG), the gatekeeper that dictates the scale and composition of glycosphingolipid diversity. Despite its biological and therapeutic importance7,8, its mechanism and regulation have remained unknown. Here we report cryogenic electron microscopy structures of full-length human UGCG in eight functional states at 2.9-3.4 Å resolution. UGCG adopts a previously unrecognized triple-pass transmembrane architecture that anchors a GT-A core at the membrane interface and creates a bipartite active site engaging soluble and membrane-embedded substrates. Contrary to canonical GT-A enzymes, UGCG uses a metal-independent catalytic mechanism driven by an arginine network. We identify a primate-specific steric element that tunes lipid affinity and catalytic turnover, modulating glycosphingolipid entry. Structures with clinically used inhibitors reveal how this architecture governs their potency and selectivity. Together, these findings define the structural and evolutionary logic by which one enzyme controls glycosphingolipid diversity and provide a framework for precision modulation of membrane lipid homeostasis in disease.

Animals↗

PubMed2025

SUG2 controls grain size and weight by influencing GS2 transcription level in rice.

Grain size is a critical yield determinant and a complex quantitative trait in rice. The major quantitative trait locus GS2, which encodes the transcriptional regulator OsGRF4, has been characterized as a key controller of grain size and grain weight in rice. Building upon existing germplasm resources, exploring the upstream and downstream genes of known grain size regulators is an effective approach to gradually refine and expand the molecular regulatory network underlying grain size. Here, we report that a suppressor of the gain-of-function allele GS2AA, SUG2, which encodes an importin β nuclear transport protein. Phenotypic characterization reveals that the sug2 GS2AA mutant exhibits small grains by inhibiting cell expansion in the spikelet hull. Protein interaction analyses demonstrate that SUG2 physically interacts with GS2 both in vivo and in vitro, and the SUG2A mutation reduces SUG2 expression levels and inhibits GS2 transcriptional activation activity, resulting in decreased GS2 expression levels and GS2 protein abundance in sug2 GS2AA. Genetic analyses indicate that SUG2 and GS2 may be partially involved in a common pathway regulating grain size and weight in rice. These findings elucidate the grain size regulatory relationship between SUG2 and GS2 and provide novel insights into the precision breeding of yield optimization in rice.

Oryza↗

PubMed2006

Establishing glucose- and ABA-regulated transcription networks in Arabidopsis by microarray analysis and promoter classification using a Relevance Vector Machine.

Establishing transcriptional regulatory networks by analysis of gene expression data and promoter sequences shows great promise. We developed a novel promoter classification method using a Relevance Vector Machine (RVM) and Bayesian statistical principles to identify discriminatory features in the promoter sequences of genes that can correctly classify transcriptional responses. The method was applied to microarray data obtained from Arabidopsis seedlings treated with glucose or abscisic acid (ABA). Of those genes showing >2.5-fold changes in expression level, approximately 70% were correctly predicted as being up- or down-regulated (under 10-fold cross-validation), based on the presence or absence of a small set of discriminative promoter motifs. Many of these motifs have known regulatory functions in sugar- and ABA-mediated gene expression. One promoter motif that was not known to be involved in glucose-responsive gene expression was identified as the strongest classifier of glucose-up-regulated gene expression. We show it confers glucose-responsive gene expression in conjunction with another promoter motif, thus validating the classification method. We were able to establish a detailed model of glucose and ABA transcriptional regulatory networks and their interactions, which will help us to understand the mechanisms linking metabolism with growth in Arabidopsis. This study shows that machine learning strategies coupled to Bayesian statistical methods hold significant promise for identifying functionally significant promoter sequences.

Abscisic Acid↗

PubMed2006

Sugar and ABA response pathways and the control of gene expression.

Sugars are essential to plant growth and metabolism, both as energy source and as structural components. Sugar production and use are in part controlled at the level of gene expression by the sugars themselves. Responses to sugar are closely integrated with response pathways that indicate environmental conditions such as light and water availability. High sugar levels inhibit seedling development, repress photosynthetic gene expression and induce genes of storage metabolism such as those of starch biosynthesis. Genetic approaches have demonstrated the importance of abscisic acid (ABA) and the transcriptional regulator ABA-insensitive4 (ABI4) in sugar response pathways. Recent analysis of both photosynthetic and starch biosynthetic gene promoters suggest a direct role for ABI4 in their control. The increased understanding of the regulatory promoter elements controlling gene expression, in response to sugar and ABA, allows transcriptional networks to be understood at a molecular level.

Abscisic Acid↗

PubMed2004

Arabidopsis NAP and PIR regulate actin-based cell morphogenesis and multiple developmental processes.

The actin cytoskeleton mediates cellular processes through the dynamic regulation of the time, location, and extent of actin polymerization. Actin polymerization is controlled by several types of evolutionarily conserved proteins, including those comprising the ARP2/3 complex. In animal cells ARP2/3 activity is regulated by WAVE complexes that contain WAVE/SCAR proteins, PIR121, Nap125, and other proteins. The activity of the WAVE complex is regulated by Rho-GTPase-mediated signaling that leads to ARP2/3 activation by WAVE/SCAR proteins. We describe in this report Arabidopsis (Arabidopsis thaliana) genes encoding Nap and PIR proteins. Light-grown Atnap-1 and Atpir-1 mutant plants displayed altered leaf, inflorescence, silique, and seed set phenotypes. Dark-grown Atnap-1 and Atpir-1 seedlings also exhibited longer roots, enhanced skotomorphogenesis and Glc responses, and shorter thicker hypocotyls than those of wild type, showing that AtNAP and AtPIR participate in a variety of growth and developmental processes. Mutations in AtNAP and AtPIR caused cell morphology defects in cotyledon pavement cells and trichomes seen in mutants in ARP2/3 subunits and in plants expressing constitutively active Rop2 GTPase. The patterns and levels of actin polymerization observed in Atnap-1 and Atpir-1 mutant trichome cells and epidermal pavement cell morphology is consistent with Arabidopsis NAP and PIR proteins forming a WAVE complex that activates ARP2/3 activity. The multiple growth and developmental phenotypes of Atnap and Atpir mutants reveals these proteins are also required for a wider variety of cellular functions in addition to regulating trichome cell growth.

Actins↗

PubMed2003

BRITTLE CULM1, which encodes a COBRA-like protein, affects the mechanical properties of rice plants.

Plant mechanical strength is an important agronomic trait. To understand the molecular mechanism that controls the plant mechanical strength of crops, we characterized the classic rice mutant brittle culm1 (bc1) and isolated BC1 using a map-based cloning approach. BC1, which encodes a COBRA-like protein, is expressed mainly in developing sclerenchyma cells and in vascular bundles of rice. In these types of cells, mutations in BC1 cause not only a reduction in cell wall thickness and cellulose content but also an increase in lignin level, suggesting that BC1, a gene that controls the mechanical strength of monocots, plays an important role in the biosynthesis of the cell walls of mechanical tissues.

Amino Acid Sequence↗