Biology subjects

Ying, Q.

Publications and source records attributed to Ying, Q..

6 recordsLinked to original sources

bioRxiv2025

SPLiCR-seq: A CRISPR-Based Screening Platform for RNA splicing Identifies Novel Regulators of IRE1-XBP1 Signaling Under ER Stress

RNA splicing is fundamental to cellular function, yet systematic investigation of its complex regulation has been limited by existing methods. Here, we present SPLiCR-seq (SPLicing regulator identification through CRISPR screening), a high-throughput CRISPR screening platform that enables direct measurement of RNA splicing outcomes for pooled genetic perturbations, overcoming limitations of traditional fluorescence-based approaches. Applying SPLiCR-seq to investigate XBP1 splicing during the unfolded protein response (UPR), we conducted targeted and genome-wide screens across diverse cellular contexts, revealing both common and cell-type specific regulators. Notably, we identified GADD34 (PPP1R15A) as a novel modulator of IRE1-XBP1 signaling, demonstrating that it directly interacts with IRE1 and functions independently of its canonical role in eIF2 dephosphorylation. Pharmacological inhibition of GADD34 using Sephin1 effectively suppressed XBP1 splicing and alleviated CAR-T cell exhaustion in an ex vivo model, leading to enhanced tumor-killing capacity across multiple cancer models. This work not only establishes a powerful new tool for systematically studying RNA splicing regulation but also uncovers a promising therapeutic strategy for improving CAR-T cell immunotherapy through modulation of the IRE1-XBP1 pathway.

genetics↗

bioRxiv2025

Selective RNA sequestration in biomolecular condensates directs cell fate transitions

Recent studies have emphasized the significance of biomolecular condensates in modulating gene expression through RNA processing and translational control. However, the functional roles of RNA condensates in cell fate specification remains poorly understood. Here, we profiled the coding and non-coding transcriptome within intact biomolecular condensates, specifically P-bodies, in diverse developmental contexts, spanning multiple vertebrate species. Our analyses revealed the conserved, cell type-specific sequestration of untranslated RNAs encoding key cell fate regulators. Notably, P-body contents did not directly reflect active gene expression profiles for a given cell type, but rather were enriched for translationally repressed transcripts characteristic of the preceding developmental stage. Mechanistically, microRNAs (miRNAs) direct the selective sequestration of RNAs into P-bodies in a context-dependent manner, and perturbing AGO2 or alternative polyadenylation profoundly reshapes P-body RNA content. Building on these mechanistic insights, we demonstrate that modulating P-body assembly or miRNA activity dramatically enhances both activation of a totipotency transcriptional program in naive pluripotent stem cells as well as the programming of primed human embryonic cells towards the germ cell lineage. Collectively, our findings establish a direct link between biomolecular condensates and cell fate decisions across vertebrate species and provide a novel framework for harnessing condensate biology to expand clinically relevant cell populations.

cell biology↗

bioRxiv2022

Multi-scale observations of mangrove blue carbon fluxes; the NASA Carbon Monitoring System BlueFlux field campaign

The BlueFlux field campaign is supported by NASAs Carbon Monitoring System (CMS) and will develop prototype blue carbon products to inform coastal carbon management. Blue carbon is included in carbon-dioxide removal actions proposed to reduce atmospheric CO2 concentrations to mitigate climate change. Due to their high productivity and carbon storage, combined with historic losses and a wide-range of beneficial ecosystem services, the restoration and conservation of mangrove ecosystems features prominently in blue-carbon planning. The goal of BlueFlux is to carry out multi-scale measurements of CO2 and CH4 fluxes using chambers, flux towers, and aircraft and scale these to gridded products using space-based observations of forest structure and surface reflectance. The measurements cover gradients in disturbance, mainly from the history of hurricanes in the region that drive the dieback of mangroves and the formation of ghost forests. The fluxes of CH4 emissions will be contrasted with CO2 uptake to provide a more complete budget of radiative forcing and to understand the net climate benefits of blue carbon. BlueFlux demonstrates that quantifying the removals of CO2 and emissions of CH4 using a multi-scale approach can provide increased confidence in regional greenhouse-gas accounting, contribute to process-understanding, and help inform restoration and conservation efforts in the context of climate mitigation.

ecology↗

bioRxiv2022

An immune-lncRNA risk model to predict prognosis for patients with head and neck squamous cell carcinoma

Backgroundlong noncoding RNA (lncRNA) are closely correlated with the occurrence and development of tumors. The purpose of this research is to construct a risk model of immune-related lncRNAs that can be used for predicting the survival and prognosis of head and neck squamous cell carcinoma (HNSCC) patients and further exploring the immune function of immune-lncRNAs. Methodsobtained detailed transcriptional data and clinical information for 545 cases of HNSCC from The Cancer Genome Atlas (TCGA). Combined lncRNAs and the immune gene sets from the Molecular Signatures Database (MSigDB) were employed to construct co{square}expression networks, the significant correlation of immune-lncRNAs obtained from the results of Cox regression analysis were used to build the model. Survival analysis and QRT-PCR were used to confirm the expression of immune-lncRNAs and optimize the risk model. Then single-cell RNA Sequencing (scRNA-seq) dataset analysis of laryngeal squamous cell carcinoma (LSCC), co-expression analysis, correlation analysis and immunohistochemistry were used to explore the immune function of immune-lncRNAs. ResultsA total of 13 immune-lncRNAs including AC104083.1AC004148.2AL357033.4AC116914.2AC024075.1AC008115.3PCED1B-AS1RAB11B-AS1AC004687.1 AL450992.2EP300-AS1AC024075.2AC136475.2 were identified to construct the risk model. In this model, low-risk patients had higher overall survival (OS, P=1.923e-12, hazard ratio=2.104, 95% CI: 1.622-2.730). AC004687.1 and PCED1B-AS1 were overexpressed in T cells and were closely related to the genes encoding major histocompatibility complex II (MHC II) molecules. And the results of QRT-PCR and immunohistochemistry showed the expression significant positively correlated with HLA-DR which is one of the MHC II classical molecules. Conclusionthe immune-associated risk model constructed by 13 lncRNAs has good prognostic value for HNSCC. AC004687.1 and PCED1B-AS1 are significant correlating to clinical characteristics and MHC II, we provide a new insight into the immune function of lncRNAs.

bioinformatics↗

bioRxiv2022

Hantaan virus replication is promoted via AKT activated mitochondria OXPHOS

Oxidative phosphorylation (OXPHOS) is a vital pathway provides ATP for intracellular activities. Here, we found that Hantaan virus (HTNV) exploited mitochondria OXPHOS to assist its replication in host cells and Protein Kinase B/AKT played a major function in this process. Inhibiting AKT activation by BEZ treatment can inhibit HTNV replication and prevent the increase of OXPHOS level caused by HTNV infection. We also found that HTNV infection can promote AKT translocation to mitochondria, where AKT phosphorylates Polynucleotide phosphorylase (PNPT). Taken together, our research demonstrates that HTNV replication exploits OXPHOS in host cells and it increases OXPHOS function by AKT-PNPT interaction in mitochondria. IMPORTANCEVirus depends on metabolic pathways in host cells to favor its replication. This is a vital process which needs complicated host-virus interaction and targeting this process is a new strategy for antiviral drug development. Hantaan virus (HTNV) is the major pathogen which causes Hemorrhagic Fever with Renal Syndrome (HFRS) in China. However, there are neither effective therapeutic drugs nor FDA-licensed vaccine against HFRS, a deeper understanding of HTNV infection characteristics is of great significance for global public health and safety. This research means to elucidate the major metabolic pathway exploited by HTNV during its replication in host cells and its underlying molecular mechanism, which can enrich our understanding about HTNV biological characteristics and pathogenesis, also provide a new view on anti-HTNV drug development.

pathology↗

bioRxiv2021

Multi-Modal Data Analysis for Alzheimer's Disease Diagnosis: An Ensemble Model Using Imagery and Genetic Features

Alzheimers disease (AD) is a devastating neurological disorder primarily affecting the elderly. An estimated 6.2 million Americans age 65 and older are suffering from Alzheimers dementia today. Brain magnetic resonance imaging (MRI) is widely used for the clinical diagnosis of AD. In the meanwhile, medical researchers have identified 40 risk locus using single-nucleotide polymorphisms (SNPs) information from Genome-wide association study (GWAS) in the past decades. However, existing studies usually treat MRI and GWAS separately. For instance, convolutional neural networks are often trained using MRI for AD diagnosis. GWAS and SNPs are frequently used to identify genomic traits. In this study, we propose a multi-modal AD diagnosis neural network that uses both MRIs and SNPs. The proposed method demonstrates a novel way to use GWAS findings by directly including SNPs in predictive models. We test the proposed methods on the Alzheimers Disease Neuroimaging Initiative dataset. The evaluation results show that the proposed method improves the model performance on AD diagnosis and achieves 93.5% AUC and 96.1% AP, respectively, when patients have both MRI and SNP data. We believe this work brings exciting new insights to GWAS applications and sheds light on future research directions.

neuroscience↗