Biology subjects

Chen, C.

Publications and source records attributed to Chen, C..

At least 163 records · Page 9Linked to original sources

bioRxiv2025

Oncogenic EGFR rewires STING-TBK1 immune machinery to license DNA damage tolerance

EGFR hotspot mutations (mEGFR), including primary L858R, exon 19 deletion, and secondary T790M, are pivotal oncogenic drivers in human non-small cell lung cancer (NSCLC). Meanwhile, NSCLC resistance to third-generation tyrosine kinase inhibitors (TKIs) is a major clinical challenge and remains mechanistically unresolved. Here, we uncover a previously unrecognized immunological mechanism whereby mEGFR exploits cGAS-STING innate immune signaling, conventionally regarded as tumor-suppressive, to sustain oncogenic signaling and therapeutic resistance. Mechanistically, mutant EGFR kinase aberrantly incorporates into STING signalosomes, directly phosphorylating STING (Y245/Y314) and TBK1 (Y577/Y677), stabilizing and hyperactivating TBK1 proteins, and establishing an unexpected and kinase loop critical for DNA damage repair. Disruption of this mEGFR-STING-TBK1 axis, genetically or pharmacologically, profoundly sensitized resistant patient-derived NSCLC organoids to chemotherapy. Combining TBK1 inhibition with cisplatin notably eradicated mEGFR-driven tumors in spontaneous and immunocompetent NSCLC murine models and patient-derived organoids. Our findings suggest a new function of cGAS-STING in the DNA damage repair program, its paradoxical exploitation by oncogenic driver mutations, and an innate immune therapeutic vulnerability in NSCLC.

cancer biology↗

bioRxiv2025

Identification and characterization of emNagⅡ, a novel β-1,2-N-acetylglucosaminidase from Elizabethkingia meningoseptica

N-Acetylglucosamine exists in various forms and linkage patterns within organisms, playing a crucial role in numerous vital biological processes. However, research focusing on {beta}-1,2-linked N-acetylglucosamine within complex biantennary N-glycans on the cell surface remain largely unexplored. Currently, there is a lack of efficient tools and methods capable of directly modifying terminal N-acetylglucosamine on living cells. In this study, we identified a novel {beta}-N-acetylhexosaminidase from Elizabethkingia meningoseptica, which demonstrated favorable enzymatic stability within a pH range of 5-8 and at temperatures from 4 {degrees}C to 37 {degrees}C. This enzyme specifically cleaves non-reducing terminal {beta}-1,2-N-acetylglucosamine, enabling direct removal of this modification from oligosaccharides and native glycoproteins. More importantly, we demonstrate for the first time that this enzyme successfully removes {beta}-1,2-linked N-acetylglucosamine on living cell surfaces. Given its microbial origin and potential utility in living cell glycan editing, we have named it emNagII or cell-surface glycan-editing N-acetylglucosaminidase (csgeNagII). Through sequence analysis and alanine scanning mutagenesis, we identified a predicted active pocket containing the catalytic residue pair Asp317-Glu318, with Asp317 being essential for enzymatic activity. In summary, our findings provide an effective and reliable method for the targeted removal of {beta}-1,2-N-acetylglucosamine on living cell surfaces, establishing a foundation for further functional studies and practical applications.

biophysics↗

bioRxiv2025

Spatially variable growth responses to warming in Atlantic Sea Scallops (Placopecten magellanicus)

Atlantic sea scallop is an important commercial species in the U.S., and its growth rate is strongly modulated by temperature. In this study, we quantified the interannual variations in scallop growth rate and thermal stress intensity in the Mid-Atlantic Bight (MAB) from 2000 to 2018. The results showed that the scallop growth rate variations were overall synchronized between the shallow (< 60 m) and deep ([≥] 60 m) MAB prior to 2015. The response of growth rate to warming in 2015 and 2016 showed marked spatial heterogeneity: scallops in the shallow subregions grew more slowly in the warm years, whereas higher temperature contributed to elevated growth rates in the deep subregions. We developed a dynamic energy budget model to explain the distinct growth rate response to warming at different depths. The model results showed that, in 2016, bottom temperatures in the shallow subregions exceeded the optimal range, limiting the energy available for growth. In contrast, warming created more favorable thermal conditions in the deep habitats. This work reveals the spatiotemporal patterns of scallop growth rates in the MAB and contributes a quantitative understanding of thermal stress and the development of science-based management strategies under future warming.

ecology↗

bioRxiv2025

Noradrenergic Modulation of an Amygdalo-thalamic Circuit

Emotional and cognitive processing rely on communication between the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC). The BLA regulates mPFC both directly and indirectly via the medial sub-division of the medial dorsal thalamus (MDm). Although the BLA projection to MDm has been established anatomically, less is known about the functional properties of this synapse. Here, using patch-clamp electrophysiology and optogenetics in ex vivo mouse brain slices, we found that BLA neurons make potent synaptic connections onto MDm neurons capable of evoking action potentials. The site of this BLA input overlaps with strong innervation from locus coeruleus norepinephrine (NE) axons. We found that NE acts via 2-adrenergic receptors to strongly reduce excitatory postsynaptic currents from BLA to MDm. NE also decreases the release probability of BLA axon terminals through a presynaptic mechanism. Postsynaptically, NE depolarizes MDm neurons and increases their tonic firing rates. These findings show that NE, whose levels are elevated during arousal and stress, can suppress transmission of affective information from BLA into MDm, thereby blunting this potent indirect pathway from BLA to mPFC. SIGNIFICANCE STATEMENTPrevious anatomical studies have suggested the importance of amygdala input to the limbic thalamus. Here, using ex vivo electrophysiology and optogenetics in adult mice, we characterize the excitatory input from basolateral amygdala to mediodorsal thalamus, revealing the potency and physiological characteristics of this input. Further, we show that the stress-related neuromodulator, norepinephrine, binds to the 2-adrenergic receptor to significantly dampen transmission of affective information carried by this synapse. These findings improve our understanding of key circuits involved in emotional processing and provide insight on how stress-induced neuromodulation may change circuit function, which is relevant to stress-related neuropsychiatric disorders such as depression, anxiety, schizophrenia, and PTSD.

neuroscience↗

bioRxiv2025

A comprehensive characterization of the phospholipid and cholesterol composition of the uncinate fasciculus in the human brain: evidence of age-related alterations

The uncinate fasciculus (UF) is a long-range association fiber tract that serves to connect the anterior temporal lobe with the orbitofrontal cortex. The UF has been implicated via neuroimaging studies in the neurobiological vulnerability to psychiatric disorders posed by a history of childhood abuse (CA), as well as in the psychopathology underlying depressive disorders. Since the myelin sheath is highly enriched in lipids, white matter (WM) dysfunction may reflect alterations in the myelin lipid profile. In fact, our previous work showed that in the anterior cingulate cortex WM, there was a specific effect of CA in the choline glycerophospholipid fatty acids (FA) involved in the synthesis of arachidonic acid. Given that the UF does not exist in rodents, its molecular properties are highly understudied and its lipid composition is virtually unknown. As such, we sought to quantify the phospholipid FA and cholesterol quantities of the human postmortem UF and measure whether we could detect lipid-related or myelin-constituent gene/protein changes associated with CA and/or depression. Fresh-frozen left hemisphere UF samples were analyzed from individuals with depression who died by suicide with a history of severe CA (DS-CA), individuals with depression who died by suicide without a history of CA (DS), and non-psychiatric control subjects who died naturally or accidentally (CTRL). Phospholipids were separated by thin-layer chromatography. FA and non-derivatized cholesterol were quantified using gas chromatography-flame ionization detection. Relative expression of myelin-constituent genes (PLP1, MAG, CNP, MOG, PLLP, MBP, and MOBP) was measured by RT-qPCR, and levels of myelin-constituent proteins (MAG, MOG, MBP, and PLP) were measured by immunoblotting. We found no robust relationships between depression or CA and any lipid measures, nor in myelin-constituent gene and protein levels. However, in the phospholipids, we observed striking age relationships that varied across fractions, with an overall pattern of increases in monounsaturates and decreases in long chain omega-6 polyunsaturates with age. In tandem, we observed that most myelin-constituent genes and proteins showed decreasing trends with age, with PLP1 and MAG showing significantly decreasing relationships. We hypothesize that the changes in lipid composition and lipid-protein interactions contribute to age-related myelin deficits and declines in cognition. The absence of group differences highlights the importance of regional specificity in molecular studies assessing neurobiological correlates of psychiatric disorders.

neuroscience↗

bioRxiv2025

Agro-STARR-seq enables in planta genome-wide enhancer discovery and AI-empowerd enhancer design

Comprehensive enhancer screening is essential for dissecting gene regulatory networks. However, methods for such screening remain limited in plants. We present Agro-STARR-seq, an in planta enhancer screening platform using Agrobacterium-mediated delivery of STARR-seq libraries into Nicotiana benthamiana leaves. In the Arabidopsis genome, we identified 14,715 sequences with enhancer activity, of which 91.59% were located outside of open chromatin regions. This largest in planta enhancer dataset to date enabled AI-assisted design of highly active synthetic enhancers. For the large N. benthamiana genome, we pre-processed the genomic DNA with an Assay for Transposase Accessible Chromatin (ATAC) procedure before the Agro-STARR-seq protocol,and found that only one-third of open chromatin exhibited enhancer activity, 76.00% of which showed no canonical H3K27ac histone marks. Footprinting analysis further enables systematic linkage of transcription factor (TF) binding to enhancer function. Overall, Agro-STARR-seq provides a novel platform for dissecting and engineering plant enhancers.

genomics↗

bioRxiv2025

Engraftment of donor phageome via fecal microbiota transplantation in recurrent C. difficile infection: a prospective observational study

1The high efficacy of fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) is often attributed to the restoration of the bacterial community. However, factors beyond bacteria, such as bacteriophages (phages), may also play a critical role in FMTs success. We aimed to evaluate the preservation of the phage community (phageome) along the FMT production process following Good Manufacturing Practices (GMP) at the Lausanne University Hospital (CHUV), and the engraftment of the phages in patients receiving FMT to treat rCDI. Samples from one donor were used to test the need for amplification and to compare spin-column versus magnetic bead purification. Then, sixteen samples, from four donations of a second healthy donor, were collected at various production stages - fresh, frozen, homogenized, and encapsulated - for phageome analysis. The phage community profiles of three patients before, at 14, and 60 days after FMT were examined to evaluate donor phage engraftment. Phages were detected in all sample types, and samples clustered by donation, indicating that the pre-processing steps did not significantly alter the phage profile. The recipients phageome prior to FMT was characterized by low diversity, each recipient being dominated by a different phage. In contrast, the profile 14 days post-FMT demonstrated the engraftment of donor-derived phages, which persisted at 60 days. Most were predicted to be temperate phages of the Caudoviricetes class infecting members of the Clostridia bacterial class, and Lachnospiraceae and Oscillospiraceae bacterial families. Our findings suggest that the CHUV production process for oral FMT capsules preserves the phage community and that donor phages successfully engraft in recipients. Further larger-scale studies and intervention trials will help elucidate the mechanisms underlying the potential of phages in FMTs efficacy.

microbiology↗

bioRxiv2025

Structural and genetic signatures of two classes of HCV E2 neutralizing face antibodies from non-human primates immunized with a recombinant E1E2

Hepatitis C continues to be a significant public health problem despite advancements in antiviral therapeutics. To eliminate this disease, an effective vaccine against new infections and re-infections is needed. However, to date only one Hepatitis C virus (HCV) envelope protein (E1E2) immunogen, developed by Chiron Inc., has been tested in a Phase I clinical trial (ClinicalTrials.gov identifier NCT00500747). To establish a benchmark for elicitation of broadly neutralizing antibodies (bnAbs) by E1E2, we previously immunized non-human primates (NHPs) with this immunogen and isolated monoclonal nAbs that exhibit neutralization potency comparable to human nAbs. Here we show that NHP nAbs, encoded by germline genes IGHV1-138*01 and IGHV4-NL_5*01 (homologs of human IGHV1-69*10 and IGHV4-59*12, respectively), recognize a relatively E2 conserved region (neutralizing face) proximal to antigenic region 3 (AR3). These NHP AR3-targeting nAbs share highly similar binding modes to human AR3-targeting nAbs, suggesting a similarity in human and NHP immune responses to the same HCV immunogen.

immunology↗

bioRxiv2025

BrAVe: a unified framework for 3D interactive and integrative analysis of cross-modal multi-scale brain atlas data in diverse species

Understanding the brain requires integrating molecular, structural, and functional information across multiple scales. Despite the rapid expansion of multimodal, multiscale brain atlases in various species, integrative analysis remains challenging. Here, we present iBrAVE, an open-source platform for 3D interactive, integrative analysis of brain atlas datasets across modalities and scales within a common reference space. iBrAVE unifies heterogeneous datasets into five core representations, enabling source-independent analyses from insects to primates. At the single-modality level, it features spatially resolved quantification, as exemplified by single-neuron morphology analyses spanning geometry, topology, projection, clustering, and putative wiring. Across modalities, it links gene expression and neuronal activity with morphologically defined neurons and putative circuits via establishing spatial correspondence. Across scales, it enables bidirectional inference of neuronal identity and synaptic connectivity between light- and electron-microscopy reconstructions via neuronal morphology matching. Thus, iBrAVE provides a unified framework for integrative brain atlas analyses, facilitating data-driven discovery in neuroscience.

neuroscience↗

bioRxiv2025

Atg16l1 promotes lung transplant tolerance by regulating glycolysis in macrophages

Lung transplant survival is limited by the development of chronic lung allograft dysfunction (CLAD), a type of graft rejection that lacks effective treatments. Autophagy plays a crucial role in maintaining cellular homeostasis. In a single-nucleotide polymorphism screen, we found that lung recipients with two copies of a common hypofunctional genetic variant of autophagy-related 16-like 1 rs2241880 (ATG16L1T300A/T300A), known to deplete this protein from macrophages, were more likely to develop early CLAD. To understand this, we used a mouse orthotopic lung transplant model. Recipients encoding myeloid cell-specific deletion of Atg16l1 (Atg16l1{Delta}/{Delta}) or who harbor an engineered orthologous mutation (Atg16l1T316A/T316A) showed similar susceptibility to CLAD. Transcript profiling and mitochondrial tracking studies indicated that increased mitochondrial damage and decreased autophagic removal of mitochondria in Atg16l1-deficient macrophages were associated with heightened activation of the hypoxia-inducible factor 1 (Hif1) pathway and accumulation of glycolytic transcripts. Metabolic analysis revealed reduced oxidative phosphorylation, increased glycolytic activity, and higher IL-1{beta} expression in Atg16l1-deficient macrophages. Notably, the development of CLAD in Atg16l1{Delta}/{Delta} lung recipients could be significantly prevented by additionally deleting Hif1 in myeloid cells or by treating with the glycolysis inhibitor 2-deoxyglucose. Our results show how a common autophagy-related genetic variant disrupts macrophage metabolism and impairs lung transplant tolerance, pointing toward potential therapeutic strategies to combat CLAD.

immunology↗

bioRxiv2025

Towards Human Inverse Dynamics from Real Images: A Dataset and Benchmark for Joint Torque Estimation

AO_SCPLOWBSTRACTC_SCPLOWHuman inverse dynamics is an important technique for analyzing human motion. Previous studies have typically estimated joint torques from joint pose images, marker coordinates, or EMG signals, which severely limit their applicability in real-world scenarios. In this work, we aim to directly predict joint torques during human movements from real human images. To address this gap, we present the vision-based inverse dynamics dataset (VID), the first dataset tailored for the joint torque prediction from real human images. VID comprises 63,369 frames of synchronized monocular images, kinematic data, and dynamic data of real human subjects. All data are carefully synchronized, refined, and manually validated to ensure high quality. In addition, we introduce a comprehensive benchmark for the vision-based inverse dynamics of real human images, consisting of a new baseline method and a new evaluation criteria with three levels of difficulty: (i) overall joint torque estimation, (ii) joint-specific analysis, and (iii) action-specific prediction. We further compare the baseline result of our VID-Network with other representative approaches, our baseline method achieves the state-of-the-art performance on almost all the evaluation criteria. By releasing VID and the accompanying evaluation protocol, we aim to establish a foundation for advancing biomechanics from real human images and to facilitate the exploration of new approaches for human inverse dynamics in unconstrained environments. The project website is https://github.com/MedVisionKitchen/VID-Benchmark.

bioinformatics↗

bioRxiv2025

Brain Region-Specific Epigenomic Reorganization and Altered Cell States in Alzheimer's Disease

Alzheimers disease (AD) is the most common neurodegenerative disorder, yet the molecular mechanisms underlying its region- and cell-type-specific pathogenesis remain poorly defined. Here, we generated a large-scale, single-cell multi-omic atlas--integrating DNA methylation and 3D genome architecture--from postmortem brain tissue of matched AD patients and cognitively normal controls. Samples were collected from three brain regions with distinct vulnerability to AD pathology: the temporal cortex (TC), primary visual cortex (VC), and prefrontal cortex (PFC). Our dataset comprises over 230,000 individual cells, spanning major neuronal and glial populations, and provides a high-resolution view of multi-layer epigenomic regulation. We identified widespread AD-associated DNA methylation changes and marked reorganization of 3D genome structure, including alterations in A/B compartments, topologically associating domains (TADs), and chromatin loops. These changes are strongly region-specific: TC displays pronounced hypermethylation, transcriptional downregulation, and elevated boundary density, whereas VC shows opposing trends and PFC an intermediate profile. We further uncovered previously unrecognized AD-associated glial and neuronal states defined by coordinated epigenomic dysregulation and recurrent genomic deletions, particularly near telomeric regions. This region-resolved, single-cell multi-omic atlas reveals divergent epigenomic trajectories across brain regions and cell types in AD, offering new mechanistic insights and a framework for targeted therapeutic strategies.

genomics↗

bioRxiv2025

Role of tankyrase scaffolding in the β-catenin destruction complex and WNT signaling

Aberrant WNT/{beta}-catenin signaling drives tumorigenesis and metastasis in cancer. Although enzymatic inhibitors of tankyrase (TNKS) effectively block AXIN degradation and stabilize the {beta}-catenin destruction complex (DC), they have demonstrated limited efficacy in various cancer models. Here we demonstrate that, unexpectedly, the induction of AXIN puncta represents a major barrier to achieving therapeutic efficacy. Mechanistically, catalytic inhibition of TNKS prevents TNKS turnover and drives its accumulation in the DC, wherein the scaffolding function of TNKS induces AXIN puncta formation, rigidifies the DC, and impedes {beta}-catenin turnover. Chemically induced degradation of TNKS overcomes this limitation by stabilizing AXIN without puncta formation, providing a deeper suppression of the WNT/{beta}-catenin pathway activity and the proliferation of colorectal cancer cells harboring dysfunctional APC mutations. Collectively, these findings provide an explanation for the unsatisfactory outcomes of drugging the WNT/{beta}-catenin signaling pathway by TNKS inhibitors and highlight TNKS degradation as a promising approach to treat WNT/{beta}-catenin-driven cancers.

cancer biology↗

bioRxiv2025

Uncovering genetic architecture of the heart via genetic association studies of unsupervised deep learning derived endophenotypes

Recent genome-wide association studies (GWAS) have effectively linked genetic variants to quantitative traits derived from time-series cardiac magnetic resonance imaging, revealing insights into cardiac morphology and function. Deep learning approach generally requires extensive supervised training on manually annotated data. In this study, we developed a novel framework using a 3D U-architecture autoencoder (cineMAE) to learn deep image phenotypes from cardiac magnetic resonance (CMR) imaging for genetic discovery, focusing on long-axis two-chamber and four-chamber views. We trained a masked autoencoder to develop Unsupervised Derived Image Phenotypes for heart (Heart-UDIPs). These representations were found to be informative to indicate various heart-specific phenotypes (e.g., left ventricular hypertrophy) and diseases (e.g., hypertrophic cardiomyopathy). GWAS on Heart UDIP identified 323 lead SNP and 628 SNP-prioritized genes, which exceeded previous methods. The genes identified by method described herein, exhibited significant associations with cardiac function and showed substantial enrichment in pathways related to cardiac disorders. These results underscore the utility of our Heart-UDIP approach in enhancing the discovery potential for genetic associations, without the need for clinically defined phenotypes or manual annotations.

bioinformatics↗

bioRxiv2025

Condensate-based shells and scaffolds via interfacial liquid-to-solid transition of disordered peptides

Living organisms use biomolecular condensates to respond to dynamic environments and create functional materials with complex architectures. Exploring such phase-separated systems beyond the naturally occurring scenarios may offer valuable insights for emergent synthetic biosystems. Here, we report the self-assembly behavior of a short, disordered peptide sequence (termed CT45) derived from a protein present in the bioad-hesive system of tick ectoparasites. We show that CT45 spontaneously accumulates at polar-nonpolar interfaces, and further undergoes liquid-liquid and liquid-to-solid phase transitions to create mechanically stable structures. When encapsulated within vesicles and presented with a stable oil-water interface, CT45 rapidly forms solid shells, which can be reinforced by up-concentrating the material through osmotic imbalance. Unex-pectedly, when presented with a transient acetone-water interface, CT45 condenses at the evaporating interface and forms interconnected, porous mesoscopic scaffolds. The underlying mechanism is found to be the amphiphilic nature of CT45 leading to in-terfacial accumulation, enhancing intermolecular{pi} -based interactions to trigger phase transitions. The micron-sized shells exhibit appreciable mechanical strength and the porous scaffolds present a highly stable platform capable of retaining molecules. In conclusion, the presented condensate-based microscopic and mesoscopic scaffolds hold significance in customizable condensate architectures, with potential applications in biomedical engineering and synthetic biology.

bioengineering↗

bioRxiv2025

Brain Preparedness for Active Forgetting: Cortisol Awakening Response Proacts Prefrontal Control Over Hippocampal-Striatal Circuitry

Stress-related psychiatric pathologies (e.g., rumination in depression, intrusive memories in PTSD) involve impaired inhibitory control over emotional memories and disrupted cortisol circadian rhythms. However, how these mechanisms interact to support adaptive forgetting remains unclear. Here, by integrating multi-modal neuroendocrine profiling with fMRI-based memory suppression in 90 participants, we demonstrate that the cortisol awakening response (CAR)--a circadian surge priming the brain for daily demands--proactively and selectively enhances suppression of recently acquired but not overnight-consolidated emotional memories. This time-dependent facilitation manifests through dual neural mechanisms: Robust CAR broadly amplifies dorsolateral prefrontal cortex (dlPFC) engagement during suppression attempts and specifically strengthens top-down dlPFC control over hippocampal-striatal circuits exclusively for recent traces. Our findings bridge circadian biology, systems neuroscience, and clinical psychopathology to establish CAR as a neuroendocrine preparedness mechanism that proactively configures adaptive forgetting circuits across sleep-wake cycles, thereby informing circadian-based interventions for stress disorders.

neuroscience↗

bioRxiv2025

Imaging progenitor cell differentiation during central nervous system remyelination using an MRI gene reporter

Demyelination, the loss of the myelin sheath from around otherwise intact axons, occurs in several diseases, most notably multiple sclerosis (MS). Demyelinated axons that are not remyelinated are vulnerable to irreversible degeneration and therefore therapies that enhance remyelination have been sought. However, there remains a paucity of suitable outcome measures to assess their efficacy. Magnetic Resonance Imaging (MRI) is a non-invasive imaging modality that is used both preclinically and clinically for the assessment of anatomy and tissue function. Here we describe an MRI technique for following the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes during the spontaneous regenerative process of remyelination in vivo. OPCs were transduced in situ with a lentiviral vector expressing an organic anion transporting polypeptide (Oatp1a1) under the control of the differentiation-specific Myelin Basic Protein (MBP) promoter. Oatp1a1 mediates cell uptake of a gadolinium-based MRI contrast agent (Primovist), allowing detection of the cells in T1-weighted MR images. Uptake of the contrast agent is restricted to MBP-expressing cells, which is most highly expressed during myelin sheath formation, thereby allowing progenitor-mediated, and potentially oligodendrocyte-mediated, remyelination to be monitored non-invasively in vivo using MRI. These findings provide the foundation for the development of direct methods for assessing the efficacy of pro-remyelination therapies.

neuroscience↗

bioRxiv2025

Aberrant host mRNA partitioning in Ebola virus condensates driven by RNA folding perpetuates species-dependent interferon response

RNA viruses form membraneless condensates in host cells to drive replication, but whether these compartments also regulate host RNAs remains unclear. Using MERFISH-based subcellular transcriptomics, we quantified cellular mRNA recruitment into Ebola virus condensates under basal and IFN-stimulated states. We find that in the basal state, cellular RNAs with minimally folded coding regions are selectively recruited. Under IFN-stimulation, however, interferon-stimulated genes (ISGs) with structured 3'UTRs concentrate in viral condensates. We find that both features, minimally folded coding regions and structured 3'UTRs, are conserved in the viral RNA genome, supporting viral genome retention in condensates. In parallel, for cellular mRNAs, we find that partitioning into condensates escapes decay, prolonging RNA-half-life, and amplifying rather than dampening ISG expression. Fruit bats, which do not experience severe disease for RNA viruses, instead have ISGs with reduced 3'UTR folding, and may evade condensate-sequestration, enabling balanced antiviral responses. This selective stabilization links condensate function to RNA regulation as a molecular determinant of viral and host co-evolution and disease pathogenesis.

microbiology↗