Biology subjects

Zhan, G.

Publications and source records attributed to Zhan, G..

4 recordsLinked to original sources

bioRxiv2026

Two ancient nuclear lineages and divergent reproductive strategies drive global success of the wheat stripe rust pathogen

Understanding the mechanisms for generating and maintaining plant pathogen genetic diversity is essential for predicting disease emergence and safeguarding the food supply. Here, using population-genomic analyses of 507 global isolates of the wheat stripe rust fungus Puccinia striiformis f. sp. tritici, we uncover two nuclear lineages that diverged before modern agriculture and reinforced during wheat domestication. Distinct lineage combinations underpin three major global populations: two predominantly sympatric, homozygous lineages (nuclA-nuclA and nuclB-nuclB) and a globally dominant heterokaryotic lineage (nuclA-nuclB) of hybrid origin. This hybrid population evolves largely clonally, accompanied by recurrent somatic nuclear exchange. Identical virulence traits can arise independently via somatic nuclear exchange in clonal populations or through sexual recombination in recombining populations, revealing convergent evolutionary routes to adaptation. Together, our results provide a transformative nuclear-level perspective linking deep evolutionary history and reproductive strategy to the global success of cereal rust fungi.

genetics↗

bioRxiv2025

ABCG transporter gene PstABCG2 contributes to multidrug resistance in Puccinia striiformis

The emergence of triadimefon resistance in Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust, poses a growing threat to global food security. While the novel SDHI fungicide flubeneteram exhibits high efficacy against Pst, the molecular mechanisms governing resistance to both fungicides remain largely unknown. Here, we identify the ABC transporter PstABCG2 as a key mediator of multidrug resistance (MDR) through combined transcriptomic, genetic, and biochemical analyses. First, time-series transcriptomics revealed sustained upregulation of PstABCG2 under fungicide stress, with silencing via in planta RNAi and HIGS significantly enhancing Pst sensitivity to both triadimefon and flubeneteram. Heterologous expression of PstABCG2 in a Fusarium graminearum {Delta}FgABCG2 mutant restored fungicide tolerance, confirming its efflux function. Crucially, saturation mutagenesis and structural modeling pinpointed E1184 as a critical residue for fungicide binding: the E1184Y mutation disrupted triadimefon affinity (validated by MST/ITC, {Delta}G reduced from -7.1 to -6.5 kcal/mol) but minimally impacted flubeneteram binding due to adaptive halogen-bond networks. Furthermore, we discovered that the GATA-family transcription factor PstGATA directly activates PstABCG2 expression by binding to promoter cis-elements, and silencing PstGATA phenocopied the hypersensitivity of PstABCG2-silenced isolates. The results may provide a theoretical foundation for elucidating multidrug resistance mechanisms in Pst, field resistance management, and novel fungicide target development.

pathology↗

bioRxiv2022

Harringtonine has the effects of double blocking SARS-CoV-2 membrane fusion

Fusion with host cell membrane is the main mechanism of infection of SARS-CoV-2. Here, we propose a new strategy to double block SARS-CoV-2 membrane fusion by using Harringtonine (HT), a small-molecule antagonist. By using cell membrane chromatography (CMC), we found that HT specifically targeted the SARS-CoV-2 S protein and host cell TMPRSS2, and then confirmed that HT can inhibit pseudotyped virus membrane fusion. Furthermore, HT successfully blocked SARS-CoV-2 infection, especially in the delta and Omicron mutant. Since HT is a small-molecule antagonist, it is minimally affected by the continuous variation of SARS-CoV-2. Our findings show that HT is a potential small-molecule antagonist with a new mechanism of action against SARS-CoV-2 infection, and thus HT mainly targets the S protein, and thus, greatly reduces the damage of the S proteins autotoxicity to the organ system, has promising advantages in the clinical treatment of COVID-19.

pharmacology and toxicology↗

bioRxiv2021

Phase separation of RNA-binding protein promotes polymerase engagement and transcription

An RNA-involved phase-separation model has been proposed for transcription control. Yet, the molecular links that connect RNA binding to the transcription machinery remain missing. Here we find RNA-binding proteins (RBPs) constitute half of the chromatin proteome in embryonic stem cells (ESCs), and some are colocalized with RNA polymerase (Pol) II at promoters and enhancers. Biochemical analyses of representative RBPs--such as PSPC1 and PTBP1--show that the paraspeckle protein PSPC1 not only prevents the RNA-induced premature release of Pol II, and also makes use of RNA as multivalent molecules to promote Pol II engagement and activity, by enhancing the phase separation and subsequent phosphorylation and release of polymerase condensates. In ESCs, auxin-induced acute degradation of PSPC1 leads to genome-wide defects in Pol II phosphorylation and chromatin-binding and nascent transcription. We propose that the synergistic interplay of RBPs and RNA aids in the rate-limiting step of polymerase condensate formation to promote active transcription.

biochemistry↗