Biology subjects

Hu, Q.

Publications and source records attributed to Hu, Q..

At least 19 recordsLinked to original sources

bioRxiv2026

A learning-to-rank framework for large-scale identification of unknown proteins from cryo-EM and cryo-ET maps

Cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) can yield density maps whose molecular identities are unknown. Predicted-structure databases enable proteome-scale searches, but distinguishing the correct candidates remains challenging, particularly for intermediate-resolution maps without clear side-chain features. We developed CryoAssign, an automated framework that combines large-scale structure matching with learning-to-rank prioritization. CryoAssign searches intact density maps without prior segmentation and integrates complementary measures of map-model agreement. On held-out benchmark maps, CryoAssign robustly prioritized the correct candidates. It also identified proteins or narrowed the set of candidates in previously unassigned cryo-EM maps and recovered multiple components from complex cryo-EM and cryo-ET maps. Controlled low-pass filtering showed generally robust recovery across a broad range of intermediate resolutions. CryoAssign provides a scalable approach for identifying proteins from cryo-EM and cryo-ET density maps.

biophysics↗

bioRxiv2026

The RNA-binding protein TRIM71 Promotes Supporting Cell Reprogramming and Hair Cell Regeneration by Activating Sall4

Hair cell (HC) loss in the auditory organ (cochlea) is irreversible and represents the leading cause of deafness in humans. The absence of HC regeneration is primarily due to the limited plasticity of cochlear supporting cells (SCs). Using a novel doxycycline-inducible TRIM71 transgenic mouse model, this study demonstrates that overexpression of the RNA-binding protein TRIM71 promotes spontaneous cochlear HC regeneration in neonatal mice. Experiments in cochlear organoids indicate that TRIM71 reprograms SCs into progenitor-like cells and that this reprogramming is further enhanced by coactivation of follistatin (FST). FST augments TRIM71-induced increases in chromatin accessibility at progenitor and HC-specific gene loci, facilitating their transcriptional activation in SCs. Notably, FST also enhances TRIM71-induced reactivation of Sall4, which, like Trim71, is highly expressed in early otic progenitors. Using cochlear organoids and explants, we show that the early otic transcription factor SALL4 is required for TRIM71-induced HC formation. By contrast, SALL4 overexpression inhibits HC formation by maintaining reprogrammed SCs in an undifferentiated, proliferative state. These findings establish TRIM71 as an activator of HC regeneration in vivo, provide mechanistic insights into TRIM71's role in SC reprogramming, and identify SALL4 as its essential effector.

cell biology↗

bioRxiv2026

Asymmetric assembly of congested contiguous stereocenters via photobiocatalytic three-component radical coupling

Despite rapid advances in new-to-nature biocatalysis, trimolecular enzymatic reactions that generate previously inaccessible molecular entities, particularly those bearing well-defined, congested stereochemical dyads, remain exceedingly rare. Here, we report a novel diastereo- and enantioselective photobiocatalytic three-component radical coupling unknown in both organic chemistry and enzymology, enabled by cooperative catalysis employing an evolved pyridoxal biocatalyst and a transition-metal photosensitizer. Directed evolution using high-throughput photobiocatalysis furnished two threonine aldolase variants, enabling the stereoselective assembly of contiguous tri- and tetrasubstituted stereocenters as well as vicinal tetrasubstituted stereocenters, which were long regarded as a challenging goal for stereoselective radical chemistry and asymmetric catalysis. Furthermore, a variety of radical precursors, including alpha-iodoesters, alpha-iodoamides, alpha-iodoketones, and alpha-iodonitriles, could be transformed into structurally diverse, densely substituted non-canonical amino acid derivatives via C-H functionalization with excellent stereocontrol. Leveraging the broad substrate compatibility of engineered pyridoxal biocatalysts, combinatorial biocatalysis was achieved by simultaneously varying all three coupling partners, delivering products with a 98% success rate. Collectively, this diversity-generating multicomponent photobiocatalytic radical coupling afforded a powerful strategy for addressing long-standing challenges in asymmetric catalysis while enabling access to valuable stereochemically complex small molecules with applications in medicinal chemistry.

biochemistry↗

bioRxiv2026

Integrated anthocyanin profiling and transcriptome analysis identify candidate genes associated with petal color variation in Cyclamen persicum

Petal coloration is a key ornamental trait in Cyclamen persicum Mill. and is closely associated with anthocyanin composition and relative accumulation, yet the major anthocyanins and candidate molecular factors associated with color variation remain unclear. In this study, anthocyanin profiling and transcriptome analysis were integrated to investigate three Cyclamen materials with distinct petal colors, BXK, FXK, and SHXK. Anthocyanin profiling showed clear separation among the three materials, indicating that petal color divergence was associated with differences in anthocyanin composition and relative abundance. Petunidin-, peonidin-, delphinidin-, malvidin-, and cyanidin-related derivatives exhibited distinct accumulation patterns. Transcriptome analysis revealed marked transcriptional divergence, with phenylpropanoid and flavonoid biosynthesis repeatedly enriched across comparisons, whereas isoflavonoid and flavone and flavonol biosynthesis were enriched in selected comparisons. Mapping differentially expressed genes onto the anthocyanin biosynthetic pathway revealed branch-specific expression patterns of structural genes, including CHS, F3H/F3'H, F3'5'H, DFR, and ANS. Notably, Cluster-26256.0, annotated as a putative anthocyanidin synthase gene, showed a progressive increase in expression from BXK to FXK and SHXK, consistent with increasing petal pigmentation. Several DFR-related transcripts also showed relatively high expression in SHXK. Co-expression analysis linked key anthocyanins, structural genes, and transcription factors, while qRT-PCR generally confirmed RNA-seq trends. These results suggest that late anthocyanin biosynthesis, particularly ANS-related transcriptional variation, may contribute to dark red petal coloration. This study provides a metabolite-transcript framework for Cyclamen petal coloration and identifies ANS-related genes as priority candidates for future functional studies and flower-color breeding.

plant biology↗

bioRxiv2026

Generative Access to Make-on-Demand Chemical Space Enables Ultra-Large Virtual Screening

Ultra-large-scale virtual screening (ULVS) increasingly relies on make-on-demand chemical spaces, but efficient access to these spaces remains challenging because their scale far exceeds what can be exhaustively enumerated and docked. Here, we present REAL-SWIT, a generative ULVS framework that learns Enamine REAL Space as a synthesizable molecular distribution and couples this generator with a target-specific scoring model to enable docking-guided exploration of REAL Space at the level of complete molecule. The generative model learned transferable features of the REAL Space distribution: approximately 96% of generated molecules were found in REAL Space, and a subset of generated molecules absent from the training release appeared in later expanded releases. In computational benchmarks, REAL-SWIT identified more molecules with favorable docking scores than representative fragment-based search strategies, including cooperative building-block combinations that fragment-level prioritization tended to miss. Experimental validation for ROCK1 yielded six biochemical inhibitors among 23 synthesized compounds, including RX-3 with an IC50 of 0.17 M. These results establish generative access to make-on-demand chemical space as a practical strategy for ULVS.

bioinformatics↗

bioRxiv2026

The mitochondrial RNA extrusion-induced innate immunity is regulated by N6-methyladenosine machinery

Mitochondrial RNA (mtRNA) released into the cytosol functions as a damage associated molecular pattern that activates pattern-recognition receptor (PRR)-mediated inflammation, yet its release mechanisms and cytoplasmic fate remain poorly understood. Here we report that chemical Abt-373-treatment and Vesicular stomatitis virus (VSV) infection induce mtRNA extrusion through Bax/Bak and VDAC1 channels, accompanied by mtDNA release. Extruded mtRNA in A549 cells activates multiple cytosolic PRRs, including RIG-I, MDA5, TLR3/7/8, and PKR, each contributing differentially to the innate immune signaling. Analysis of GEO datasets and methylated RNA immunoprecipitation (MeRIP) assays further reveals that mtRNA carries methyladenosine (m6A) modification. m6A machinery proteins are involved in the cytoplasmic retention time of mtRNA and its interaction with RIG-I, thereby modulating mtRNA-induced innate immunity. Thus, our work establishes in vitro models of mtRNA extrusion, and highlights m6A-dependent modulation as a potential therapeutic target for mtRNA-driven inflammation.

immunology↗

bioRxiv2026

Adenine nucleotide translocase 2 (ANT2) deficiency reprograms ferroptosis in alveolar progenitor cells to promote emphysema

Stem cell dysfunction and loss of renewal capacity are primary characteristics of tissue aging and decremental regeneration in response to injury. Alveolar type 2 cells (AT2) are key progenitor cells responsible for lung repair and are thought to be dysfunctional in diseases such as chronic obstructive pulmonary disease (COPD). AT2 cells are highly metabolic and rely on mitochondria, but how mitochondrial mechanisms influence their maintenance and cell fate is unclear. This gap is critical as no current therapies target lung repair or mitochondrial function in COPD. Here, we report that adenine nucleotide translocase 2 (ANT2), a key ATP/ADP transporter, is reduced in AT2 cells from COPD lungs, and that ANT2 loss impairs bioenergetics (ATP). We also identify, for the first time, ferroptotic susceptibility as a consequence of ANT2 loss in AT2 cells, leading to impaired self-renewal and progenitor capacity in alveolar organoids. Together, loss of ANT2 and the associated cellular dysfunction resulted in worsened lung damage or emphysema due to cigarette smoke in mice. Therapeutic restoration of ANT2 expression resulted in renewed AT2 stem cell function and prevention of emphysema by reducing oxidative stress and ferroptosis. These findings highlight the importance of ANT2 in metabolic regulation, plasticity, and cell resiliency of AT2 cells in the lung and that ANT2 is a potential target for lung repair. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/737954v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@7193bborg.highwire.dtl.DTLVardef@9a0446org.highwire.dtl.DTLVardef@18e9f5corg.highwire.dtl.DTLVardef@805a05_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2026

A single chromosome 3p break initiates clear cell renal cell carcinoma evolution

Clear cell renal cell carcinoma (ccRCC) is initiated by chromosome 3p loss, yet chromosome losses impose a profound fitness burden on normal cells. How renal epithelial cells tolerate this deleterious aneuploidy during early tumorigenesis remains unclear. Analysis of 949 ccRCC genomes reveals two major classes of chromosome 3p alterations: simple deletions and complex rearrangements surrounding a terminal breakpoint - a pattern we term breakpoint-confined chromothripsis. We modeled both alterations in non-transformed human renal proximal tubule epithelial cells by introducing a single DNA double-strand break on chromosome 3p. Despite an initial fitness disadvantage, chromosome 3p loss drives adaptive genomic evolution that recapitulates recurrent ccRCC-associated aneuploidies, including 5q gain and 14q loss. These alterations alleviate the fitness constraints of 3p loss and promote metabolic reprogramming, clonal expansion, and malignant transformation, producing tumors with features of ccRCC. Thus, a single chromosome break initiates the evolutionary trajectory of ccRCC by creating a fitness bottleneck that selects for recurrent aneuploidies.

cancer biology↗

bioRxiv2026

Lifespan Analysis of the Lung Epithelium Reveals Inflammatory Reprogramming and Regenerative Decline

Aging is a major risk factor for chronic lung diseases, associated with chronic low-grade inflammation (inflammaging) and impaired epithelial regeneration. How epithelial-intrinsic aging intersects with inflammaging across the lifespan remains poorly understood. Here, we systematically analyzed lung epithelial cells from neonatal, young adult, and aged mice to define age-dependent changes in regenerative capacity. RNA sequencing revealed lifespan-associated shifts characterized by early repression of developmental and WNT/{beta}-catenin programs and progressive activation of DNA damage, inflammation, and senescence signatures. Functionally, neonatal epithelial cells exhibited markedly enhanced organoid-forming capacity compared with young and aged cells. Aged organoids maintained a pro-inflammatory secretory profile indicative of cell-intrinsic inflammaging, and transfer of the aged secretome or TNF- to young cultures significantly impaired regeneration. Comparison of freshly isolated cells and long-term organoid cultures revealed sustained repression of regenerative pathways with age, consistent with stable epigenetic imprinting. Pharmacological inhibition of DNA methylation and WNT signalling partially restored regenerative capacity in adult organoids. Together, these findings identify epigenetic reprogramming and epithelial-intrinsic inflammaging as key determinants of age-dependent regenerative decline.

cell biology↗

bioRxiv2026

Alveolar Epithelial Cell Loss of the Mitochondrial Regulator TFAM Drives Progressive Lung Fibrosis

Idiopathic pulmonary fibrosis (IPF) is characterized by failed alveolar epithelial repair and progressive fibrotic remodeling. Although aberrant reprogramming of alveolar type 2 (AT2) cells and accumulation of transitional AT2 states are increasing recognized as central features of IPF, the epithelial-intrinsic mechanisms that initiate these pathogenic states remain incompletely understood. Here, we identify mitochondrial transcription factor A (TFAM), a regulator of mitochondrial DNA maintenance, as a critical regulator of AT2 cell homeostasis. TFAM expression was reduced in AT2 cells from human IPF lungs. Inducible AT2 cell-specific Tfam deletion in mice caused spontaneous fibrotic remodeling and increased susceptibility to bleomycin-induced lung injury. TFAM-deficient AT2 cells acquired KRT8+ transitional and p21+ senescence-associated features before the onset of fibrotic transformation, accompanied by impaired oxidative phosphorylation, redox imbalance, mitochondrial superoxide accumulation, repression of mtDNA-encoded respiratory genes, and disrupted mitochondrial ultrastructure. TFAM-deficient AT2 cells developed a profibrotic secretory program that promoted extracellular matrix deposition and fibroblast activation. We further identified insulin-like growth factor-binding protein 2 (IGFBP2) as a secreted mediator induced in TFAM-deficient AT2 cells. IGFBP2 was elevated in AT2 cells in human IPF lung tissue and bronchoalveolar lavage fluid (BALF) from patients with IPF. IGFBP2 was detected in supernatants from fibrotic human precision-cut lung slices (hPCLS). IGFBP2 neutralization attenuated profibrotic remodeling in fibrotic hPCLS. Collectively, our findings identify TFAM-dependent mitochondrial homeostasis as an epithelial checkpoint linking AT2 cell-state stability to impaired epithelial-mesenchymal crosstalk driving pulmonary fibrosis.

pathology↗

bioRxiv2026

Spatiotemporal remodeling of cytoskeletal and junction networks during somatic cell reprogramming

Summary/AbstractReprogramming somatic cells into induced pluripotent stem cells involves a dramatic reorganization of the cytoskeleton and junctions during the critical mesenchymal-to-epithelial transition stage. While protein abundance changes have been profiled, the spatiotemporal dynamics of protein-protein associations involving these structural components remain poorly resolved. Here, we present a time-resolved proximity proteomics resource that maps cytoskeletal and junctional remodeling across 27 baits during the early stages of reprogramming. We identified over 1100 high-confidence interactions, including many not previously reported, capturing the dynamic reorganization of cell architecture. By integrating proximity-dependent biotinylation with quantitative proteomics, we distinguished spatial relocalizations from abundance-driven effects. Dynamic redistributions of actin regulators and desmosomal proteins were observed, and a targeted short interfering RNA screen uncovered early acting structural proteins essential for colony formation. Our findings reveal adhesion and cytoskeletal maturation as structural bottlenecks in reprogramming and provide a broadly applicable framework for mapping subcellular remodeling during dynamic cell fate transitions.

systems biology↗

bioRxiv2026

Aptamer charge-amplified field-effect transistor biosensors achieve picomolar detection limits for small-molecule biomarkers in complex biological matrices

Aptamers are attractive receptors for small-molecule biomarker detection in complex samples because of their high stability, affinity, and specificity, but aptamer-based sensors generally lack the sensitivity to detect low-abundance analytes. As a solution, we developed the charge-amplified FET (CAFET) aptamer biosensor, which is designed to amplify the net charge variation within the Debye length that occurs as a consequence of aptamer-target binding. Our sensor utilizes a strand-displacement aptamer switch, which releases an initially-hybridized displacement strand (DS) upon target binding and thus induces a measurable net charge variation within the Debye length that is amplified to a large FET current response as signal readout. This signal can be further enhanced by adding a charge label to the DS. As a consequence, our sensor can achieve far greater sensitivity than previously described aptamer-FET sensors, where the binding-induced local charge variation is modest. We demonstrate 3-hydroxykynurenine and progesterone detection with a picomolar limit of detection in undiluted human plasma--four orders of magnitude lower than the dissociation constant (KD) of the aptamer component. The CAFET sensor design is modular and should be adaptable for the detection of a wide range of clinically-informative low-abundance analytes in complex samples.

bioengineering↗

bioRxiv2026

Mapping Individualized Developmental Imbalance in Youth and Its Association with Psychopathology

The emergence of psychiatric symptoms during adolescence is increasingly hypothesized as arising from maturational imbalance across brain systems. However, this concept largely lacks quantitative grounding, which requires measuring fine-grained imbalance patterns that accurately capture acceleration or delay relative to normative developmental trajectories of brain regions. To address this gap, we leverage predictive normative modeling to learn models that predict chronological age from regional multivariate functional connectivity patterns. We demonstrate that these region-specific models are highly generalizable across independent cohorts and capture greater developmental effects than traditional functional connectivity metrics. From these models, we then derive a region-wise Relative Maturity (RM) index that quantifies individualized, region-specific deviations from normative development. Rigorous cross-cohort and longitudinal evaluations across four datasets show that RM maps are reproducible, subject-specific fingerprints of neurodevelopmental imbalance. These fingerprints are organized along continuous, low-dimensional axes aligned with intrinsic functional gradients and can predict dimensions of psychopathological vulnerability. Together, our findings establish RM as a robust, sensitive, and generalizable framework for quantifying individual vulnerability to psychopathology through system-level patterns of developmental imbalance.

neuroscience↗

bioRxiv2026

ExMODE: A Multi-Omics Repository for Extremophile Adaptation and Bioprospecting

Extreme environments, though hostile to most life forms, host specialized extremophile communities that have redefined biological cognition and emerged as vital biotechnological resources, with their unique adaptive traits and bioactive molecules driving advances in multiple scientific and industrial fields. However, research on extremophiles is hindered by limitations in culture-based methods, fragmented multi-omics data with non-uniform annotation standards across repositories, the lack of cross-extreme comparative research in existing resources, and the singularity of data dimensionality that neglects key structural information, all of which restrict the functional interpretation of extremophile microbes and the exploitation of their bioprospecting potential. To tackle these challenges, we developed ExMODE (https://db.genomics.cn/exmode/), a comprehensive multi-omics database platform dedicated to extremophiles. It centrally integrates multi-omics data from diverse extreme habitats with a standardized annotation framework, resolving data fragmentation and enabling systematic cross-environment comparative analyses to elucidate extremophile adaptive mechanisms. Moreover, ExMODE aggregates multi-dimensional datasets including genes, genomes, secondary metabolite sequences and protein structures, overcoming the constraints of single-dimensional data and significantly improving the efficiency of biotechnological resource discovery from extreme microorganisms.

microbiology↗

bioRxiv2026

Dormant Bacteria's Fatal Attraction to RNA Bacteriophages

Phages are the most abundant biological entities on Earth, yet RNA phages are strikingly scarce compared to their DNA counterparts--a long-standing mystery in phage biology. Here, we use dsRNA phage phiYY as a model to demonstrate that while RNA phages efficiently infect growing bacteria, they are gradually eliminated inside dormant bacteria through weak and time-dependent ROS-mediated damage. The RNA phages decline over days rather than through immediate clearance inside dormant bacteria. Accordingly, scavenging ROS with mannitol or overexpressing ROS degradation enzymes AhpB/TrxB2 rescues RNA phages from elimination. Crucially, because the underlying ROS-mediated RNA damage is minimal, RNA phage survival hinges on genomic redundancy. In single-phage infections, the lone RNA genome is highly vulnerable to cumulative damage and is eventually inactivated. In contrast, during co-infection by multiple RNA phages, the presence of multiple genome copies provides functional redundancy, thereby allowing a fraction of RNA phages to survive inside dormant bacteria. Given that most environmental bacteria are dormant and subject to heterogeneous phage infection, this copy number-dependent vulnerability offers a possible explanation for the scarcity, but not perish, of RNA phages in nature.

microbiology↗

bioRxiv2026

Local IFNγ signaling contributes to the regenerative decline of aged alveolar progenitor cells

The lungs are highly susceptible to chronic disease in advanced age, likely due to the uniquely compromised repair function of alveolar type II (AT2) cells, facultative progenitor cells that maintain the gas exchange surface. Using aging mouse models, single-cell sequencing, and ex vivo organoid assays, we found that homeostatic aged AT2 cells exhibited an Interferon {gamma} (IFN{gamma}) response associated with IFN{gamma}+ CD8+ T cells in tertiary lymphoid structures (TLS). Aged AT2 cells exhibit impaired regeneration in organoid assays and lost markers of an IFN{gamma} response outside the lung microenvironment, demonstrating that elevated local IFN{gamma} influences the state of AT2 cells. Neutralization of IFN{gamma} signaling and immunoproteasome knockout mice with attenuated IFN{gamma} levels partially rescued aged AT2 cell regeneration. Our findings demonstrate that local IFN{gamma} signaling in aging lungs actively represses alveolar regeneration, establishing chronic inflammatory signaling as a cause of age-related decline in the lung. Halting chronic inflammatory processes restored alveolar regeneration and may provide a means to improve lung health in old age.

cell biology↗

bioRxiv2026

Mechanistic insight into the phosphorylation of ERK by MEK

The RAS-RAF-MEK-ERK cascade regulates critical cellular processes such as cell proliferation and differentiation, with its dysregulation driving over 30% of human cancers. However, the active state of MEK and molecular mechanisms of ERK phosphorylation remain unclear. Here, we report the cryo-EM structures of phosphorylated MEK1 (pMEK1) bound to unphosphorylated and monophosphorylated ERK1. These structures reveal that pMEK1 interacts with ERK1 via three interfaces: first between MEK1 N-terminal peptide and ERK1 D-site recruitment site (DRS), second between MEK1 C-lobe and ERK1 F-site recruitment site (FRS), and third between MEK1 activation loop and ERK1 activation loop. Notably, we identify an unexpected phosphorylation mechanism: pMEK1 catalyzes ERK1 T202 phosphorylation through phosphate transfer from ERK1 Y204. In addition, pMEK1 exhibits phosphatase activity, catalyzing the dephosphorylation of ERK1 Y204. These findings allow us to delineate the catalytic cycle of MEK-catalyzed ERK phosphorylation and provide insights for targeting this oncogenic pathway.

molecular biology↗

bioRxiv2026

The m6A Landscapes on the RNA of Mumps Virus and the Host 3 Modulate the Viral Replication and Antiviral Innate Immunity

N6-methyladenosine (m6A) is the most prevalent internal modification in eukaryotic mRNA and has emerged as a critical regulator of RNA virus infection. However, its role in the mumps virus (MuV), a non-segmented negative-strand (NNS) RNA virus, remains undefined. Here, we comprehensively characterize the m6A epitranscriptome of MuV JL2 strain and its functional impact on viral replication and host innate immunity. Using single-base resolution GLORI-seq, we identified abundant m6A modifications on MuV genomic, antigenomic and messenger RNAs, with uneven distribution and non-canonical motif enrichment. Genetic depletion of METTL3 enhanced viral replication by facilitating RNA synthesis and nucleocapsid encapsidation in Vero-E6 cells. In epithelial A549 and monocytoid THP1-iDC cells, MuV infection triggered robust type I/III interferon and proinflammatory responses by activating multiple pattern recognition receptors in a m6A-dependent manner and induced incomplete iDC maturation characterized by downregulated HLA class II; however, the latter molecule can be partially restored by METTL3-knockdown. The MuV infection reshaped the host m6A landscape with a positive correlation between m6A enrichment and transcripts enhancement of numerous innate immune genes in a cell type-specific manner. Functional analyses revealed that host m6A machinery modulates antiviral signaling, which varies between viral infection and viral RNA-transfection due to the infection-induced host m6A machinery fluctuation. Collectively, our findings demonstrate that m6A serves as a bidirectional regulator during MuV infection, simultaneously constraining viral replication and modulating host immune recognition, thereby highlighting RNA methylation as a pivotal determinant of MuV pathogenesis and a potential target for optimized immunogenicity. ImportanceN6-methyladenosine (m6A) modification has emerged as a key regulator of RNA virus infection, yet its role in mumps virus (MuV) remains undefined. Here we map the single-base resolution m6A landscape of a recombinant MuV and demonstrate that viral m6A restricts genome encapsidation and replication while attenuating innate immune sensing. MuV infection extensively remodels host m6A profiles in epithelial and dendritic cells, preferentially enhancing methylation of innate immune transcripts. Strikingly, m6A-deficient MuV RNA exhibits increased affinity for RIG-I-like and Toll-like receptors, eliciting stronger interferon and proinflammatory responses. Our findings identify m6A as a bidirectional regulator of MuV replication and immunity and suggest an epitranscriptomic strategy to optimize live-attenuated vaccine design.

immunology↗