Biology subjects

Lang, B.

Publications and source records attributed to Lang, B..

18 recordsLinked to original sources

bioRxiv2026

A deep learning-generated hASIC1a miniprotein inhibitor confers neuroprotection in stroke

Ion channels remain notoriously recalcitrant drug targets despite their extensive pathophysiological significance. Acid-sensing ion channels (ASICs) are proton-gated cation channels that cause neuronal death when excessively activated, such as during ischaemic stroke. This acidosis-driven injury pathway remains unchallenged by existing therapeutics. Here we generate two de novo designed hASIC1a-specific miniproteins by developing a platform that integrates computational miniprotein design, high-throughput automated patch clamp screening, biophysical and structural characterisation, and in vivo validation. We identify a subtype-selective hASIC1a inhibitor, Denasin1, which achieves near-complete inhibition with nanomolar potency. Denasin1 is disordered in solution but adopts the computationally predicted helix-turn-helix fold when bound to the extracellular acidic pocket of hASIC1a. Crucially, Denasin1 reduces infarct volume by > 50% in a murine model of ischaemic stroke. We thereby establish our de novo design platform as a route to develop potent and selective ion channel modulators.

biophysics↗

bioRxiv2026

Metatranscriptomic Identification of Co- and Incidental Infections in Marine Turtles Reveals Complex Disease Aetiologies

Traditional veterinary pathology investigations on wild animals generally conclude a primary cause of death based on a combination of observed clinical signs, gross and microscopic lesions, microbial culture and PCR. However, these methods may fail to capture the broader microbial community of the host. We employed metatranscriptomic sequencing to characterise the potential pathobiome of necropsied marine turtles, comparing these findings with corresponding veterinary pathology reports. Tissue samples were collected from 76 individuals spanning three species of marine turtles -- the green turtle (Chelonia mydas), the hawksbill turtle (Eretmochelys imbricata), and the loggerhead turtle (Caretta caretta) -- across the coastline of New South Wales, Australia. Reported causes of mortality ranged from infectious disease to trauma. We identified a diverse range of parasites within the genera Neospirochis, Hapalotrema, Paraorgymatobothrium, Eimeria and Callitetrarhynchus, and bacteria including the genera Aeromonas, Clostridium, and Vibrio. Novel viruses of the families Astroviridae, Caliciviridae, Hepaciviridae, Hepeviridae, Nyamivirdae, Orthomyxoviridae, Picobirnaviridae and Rhabdoviridae were also identified. In cases where infectious disease was noted in the pathology report, we frequently observed high pathogen read counts consistent with the listed primary diagnoses. However, we also detected a range of incidental infections involving eukaryotic parasites, bacteria, and viruses. The diversity of infectious agents detected in marine turtles suggests that the observed disease outcomes are unlikely to be driven by a single causative agent, but rather by complex interactions between host health, the pathobiome, and environmental stressors. We discuss the potential implications for turtle health and conservation.

molecular biology↗

bioRxiv2026

Rapid assessment of nitrification inhibitor efficacy, competitiveness, and specificity using microrespirometry

Nitrification inhibitors are applied to reduce nitrogen losses and greenhouse gas emissions from fertilized agricultural ecosystems. However, their characterization is typically focused on determining effective inhibitor concentrations from growth or substrate conversion assays that are time-intensive and provide limited mechanistic resolution. Here, we present a microrespirometry (MR)-based workflow for rapid mechanistic characterization of nitrification inhibitors using oxygen consumption as a real-time readout for metabolic activity. The workflow enables the simultaneous assessment of inhibitor efficacy, competitiveness, and enzyme specificity within a single experimental setup, as sequential substrate and inhibitor additions enable direct discrimination between competitive and non-competitive inhibition and between ammonia monooxygenase-specific and broader respiratory inhibition. As a proof of concept, we evaluated three known nitrification inhibitors phenylacetylene (PA), nitrapyrin (NP), and dicyandiamide (DCD) using the ammonia-oxidizing bacteria Nitrosomonas europaea and Nitrosospira multiformis, the complete ammonia oxidizer Nitrospira inopinata, and the nitrite oxidizer Nitrospira moscoviensis. We also compared the results from the MR-based inhibition workflow with those from a conventional growth-based approach and observed a poor correlation between results for inhibitors that are not fully enzyme specific. In conclusion, this work establishes MR as a rapid and versatile platform for the mechanistic screening of novel potential nitrification inhibitors. MR assays reproduce known inhibitory responses while substantially reducing experimental time and increasing mechanistic resolution compared to other assays types. Additionally, we provide the first pure-culture characterization of PA, NP, and DCD efficacy and inhibition mechanisms in a complete ammonia oxidizer, N. inopinata.

microbiology↗

bioRxiv2026

STING-STAT3-SOX18 Axis Drives EndMT and Epigenetic Reprogramming in SAVI Lung Fibrosis

A high prevalence of early-onset interstitial lung disease, including pulmonary fibrosis, in pediatric patients with Stimulator of interferon genes (STING)-Associated Vasculopathy with onset in infancy (SAVI) suggests a critical role for the cGAS-STING pathway in the pathogenesis of pulmonary fibrosis. We identified an endothelial-to-mesenchymal transition (EndMT) signature in lesional lung biopsies from SAVI patients, marked by a loss of endothelial and acquisition of mesenchymal markers. Consistently, induced pluripotent stem cell-derived endothelial cells (iECs) from SAVI patients harboring gain-of-function STING1 mutations spontaneously undergo EndMT, a process rescued in isogenic-correction. In endothelial cells, STING activation induces IRF3-independent STAT3 phosphorylation, initiating a SLUG-dependent mesenchymal transcriptional program while repressing SOX18 and an epigenetically-regulated endothelial maintenance network. Our studies define a non-canonical cGAS-STING-STAT3 signaling axis that couples a mesenchymal transcriptional program with epigenetic silencing of an endothelial maintenance program, promoting TGF{beta}-independent STING-mediated EndMT and endothelial dysfunction, and suggesting STING as a therapeutic target for inflammatory pulmonary fibrosis.

cell biology↗

bioRxiv2025

Viral diversity, ecological interconnectedness, and the identification of mammalian chuviruses in Australian microbats

Microbats are a large and ecologically important group of Australian mammalian fauna. However, their RNA virome diversity, as well as its ecological and evolutionary significance, has received limited study. We applied a metatranscriptomic approach to reveal more of the diversity of RNA viruses present in faeces from different microbat species in New South Wales and South Australia, including the critically endangered Southern bent-wing bat (Miniopterus schreibersii bassanii) from the Naracoorte bat maternity caves in South Australia. The data generated revealed a high diversity of RNA viruses, including 51 likely mammalian-associated viruses classified into ten taxonomic groups, including the Coronaviridae, Hepeviridae and Chuviridae. Notably, we identified a mammalian-specific lineage of chuviruses associated with bats in Australia and of bats and rodents in China, strongly suggesting that viruses of this family have established sustained transmission cycles in mammals as well as invertebrates. Our results also revealed widespread viral connectivity among alphacoronaviruses across multiple microbat species in mainland Australia and Christmas Island, indicative of long distance viral movement. High viral diversity and virus co-circulation was observed within the Southern bent-wing bat population of the Naracoorte caves, suggesting complex population dynamics that might facilitate virus maintenance and transmission. Overall, these findings highlight the role of Australian microbats as viral reservoirs, including the presence of viruses not previously associated with sustained mammalian transmission.

microbiology↗

bioRxiv2025

Towards Fully Automated Investigation of Social Learning in Mice

Mice have been demonstrated to learn from each other in social interactions, the extent to which this takes place and the strategies involved, however, largely remain to be elucidated beyond spatially and temporally confined tests of social memory retention. Here, we present a method which utilizes and modifies 1) a commercially available tool for automated behavioral testing, the IntelliCage and 2) an open-source solution for 24/7 live animal tracking, the Live Mouse Tracker, to create a powerful method for the investigation of learning behavior in semi-naturalistic group settings. We see a wide range of possible applications, such as for instance the investigation of learning in social interactions, which we present here as an example. In the present study, co-learning did not facilitate place learning over individual learning. While automated annotation of behaviors was effective, markerless animal identification proved unreliable in a highly enriched environment with manifold opportunity of occlusion from video tracking. In response, we here present a rationale for identifying the reliable portion of tracking data, to which we confine the behavioral analysis. Co-learning animals engaged more often in some prosocial interactions with their teammates than with other animals, but they did overall not interact with each other more frequently than with individual learners. Correlative analysis of learning behavior and social interactions did not reveal any particular association between behavior and learning success. While the mechanisms of social learning in mice could not be conclusively elucidated within the scope of this study, we report on the development of a promising tool for presenting manifold learning tasks to mice while tracking their individual and social behaviors in a fully automated manner. Further, we discuss limitations of the current configuration and present an outlook on further improving the method.

animal behavior and cognition↗

bioRxiv2025

Protein Dynamics at Different Timescales Unlock Access to Hidden Post-Translational Modification Sites

Post-translational modifications (PTMs) alter the proteome in response to intra- and extracellular signals, providing fundamental information processing in development, homeostasis and disease1-5. Here, we used proteome-wide structure predictions to investigate the structural context of protein modification sites and found nearly a fifth to be buried within proteins6. These cryptic sites within folded domains showed evolutionary conservation across species, as well as significantly less variability within the human population. We also found significantly more modification sites to be affected by recurrent cancer mutations and disease variants, with some variants appearing to mimic the modified or unmodified state, supporting their functionality and disease relevance. To understand how these buried sites become modified, we studied 23 phosphorylation sites across seven proteins using all-atom molecular dynamics simulations. The simulations revealed a range of mechanisms spanning broad timescales, ranging from picosecond fluctuations to seconds for proline isomerisation-gated phosphorylation sites. Notably, some sites remained fully buried in the native structure. Some conformational states with exposed cryptic sites resembled structures of co-translational protein folding intermediates formed on the ribosome7, indicating an interplay between protein biogenesis, folding, modifications, and signalling. We propose more broadly that protein conformational fluctuations may serve as structure-specific regulatory mechanisms by kinetically burying or exposing the unmodified, and in some cases even modified, sidechains, thereby expanding the functional versatility of proteins and enabling signal transduction across diverse timescales.

bioinformatics↗

bioRxiv2025

AlphaSync is an enhanced AlphaFold structure database synchronized with UniProt

Synchronizing protein structure predictions with sequence databases is crucial for their accuracy. We developed AlphaSync (alphasync.stjude.org), a pipeline and database that provides updated AlphaFold structure models for currently 39,961 UniProt proteins, including isoforms. Moreover, AlphaSync enhances 2.6 million structures with residue-level features, including solvent accessibility, dihedral angles, intrinsic disorder predictions, and 4.7 billion atom-level noncovalent contacts. AlphaSyncs user-friendly interface enables structural analyses at scale across up-to-date proteomes for 42 species.

bioinformatics↗

bioRxiv2025

Proteome-wide computational analyses reveal links between protein condensate formation and RNA biology

Biomolecular condensates mediate dynamic compartmentalization of cellular processes. The multivalent interactions that underlie biomolecular condensation are often promoted by intrinsically disordered regions (IDRs) within proteins. While the role of IDRs in biomolecular condensates is well appreciated, predicting whether an IDR forms condensates in cells remains challenging. Here, we developed a machine learning model to predict condensation behavior of IDRs, analyzing 215 IDRs from fusion oncoproteins in HEK293T cells. Our study identified distinct sequence-derived physicochemical features associated with condensation. Leveraging these data, our model predicts that [~]12% of the [~]13,000 IDRs in the human proteome are likely to form cellular condensates. Proteins with condensate-forming IDRs are enriched in functions involving RNA-related processes and membrane-less organelles (MLOs), highlighting their role in MLO assembly and function. Our model, available via the SAK3.0 web server (https://sak.stjude.org), provides a powerful resource for studying IDR-driven phase separation across proteomes, offering insights into biomolecular condensates and their biological roles.

bioinformatics↗

bioRxiv2023

Development and Application of Home Cage Monitoring in Laboratory Mice and Rats: a Systematic Review

Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside their home cages at selected time points. However, the outcome of such tests can be influenced by the novel environment, the time of day, separation from the social group, or the presence of an experimenter. Moreover, valuable information may be missed when the animals are only monitored in short periods. These issues can be overcome by longitudinal monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state of the art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science. Both the absolute ([~] x26) and relative ([~] x7) number of HCM-related publications increased from 1974 to 2020. In both mice and rats, there was a clear bias towards males and individually housed animals, but during the past decade (2011-2020), an increasing number of studies used both sexes and group housing. More than 70 % of the studies did not involve a disease model, but the percentage of studies using disease models increased since the 2000s. In most studies, animals were kept for short (up to 4 weeks) length periods in the HCM systems; intermediate length periods (4-12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 hours, while 24-hour measurements have been more frequently since the 2000s. The systematic review demonstrated that manual monitoring is decreasing but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the publication year, the main behavioral parameters measured were locomotor activity, feeding, and social behaviors; the main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters could be investigated in the home cage in recent times. Over the period covered in this study, techniques for HCM of mice and rats has improved considerably. This development is ongoing and further progress and validation of HCM systems will extend the applications to allow for continuous, longitudinal, non-invasive monitoring of an increasing range of parameters in group-housed small rodents in their home cages.

animal behavior and cognition↗

bioRxiv2022

Improved discovery of RNA-binding protein binding sites in eCLIP data using DEWSeq

Enhanced crosslinking and immunoprecipitation (eCLIP) sequencing is a powerful method for transcriptome-wide detection of binding sites of RNA-binding proteins (RBPs). However, identified crosslink sites can profoundly deviate from experimentally established functional elements of even well-studied RBPs. Current peak-calling strategies result in low replication and high false-positive rates. Here, we present the R/Bioconductor package DEWSeq that makes full use of replicate information and size-matched input controls. We benchmarked DEWSeq on 107 RBPs for which both eCLIP data and RNA sequence motifs are available and were able to more than double the number of motif-containing binding regions relative to standard eCLIP processing (2.3-fold median). The improvement not only relates to the number of binding sites (e.g., 3.1-fold of known motifs for RBFOX2), but also their subcellular localisation (e.g., 1.9-fold of mitochondrial genes for FASTKD2) and structural targets (e.g., 2.2-fold increase of stem-loop regions for SLBP). DEWSeq therefore shows promise as an improved processing method for eCLIP protein-RNA interaction data.

molecular biology↗

bioRxiv2021

Conserved induction of distinct antiviral signalling kinetics by primate interferon lambda 4 proteins

Interferon lambdas (IFN{lambda}) (also known as type III IFNs) are critical cytokines that combat infection predominantly at barrier tissues, such as the lung, liver and gastrointestinal tract. Humans have four IFN{lambda}s (1-4) where IFN{lambda}1-3 show [~]80-95% homology and IFN{lambda}4 is the most divergent displaying only [~]30% sequence identity. Variants in IFN{lambda}4 in humans are associated with the outcome of infection, such as with hepatitis C virus. However, how IFN{lambda}4 variants impact cytokine signalling in other tissues and how well this is conserved is largely unknown. In this study we address whether differences in antiviral signalling exist between IFN{lambda}4 variants in human hepatocyte and intestinal cells, comparing them to IFN{lambda}3. We demonstrate that compared to IFN{lambda}3, wild-type human IFN{lambda}4 induces a signalling response with distinct magnitudes and kinetics, which is modified by naturally-occurring variants P70S and K154E in both cell types. IFN{lambda}4s distinct antiviral response was more rapid yet transient compared to IFN{lambda}1 and 3. Additionally, divergent antiviral kinetics were also observed using non-human primate IFN{lambda}s and cell lines. Furthermore, an IFN{lambda}4-like receptor-interacting interface failed to alter IFN{lambda}1s kinetics. Together our data provide further evidence that major functional differences exist within the IFN{lambda} gene family. These results highlight the possible tissue specialisation of IFN{lambda}s and encourage further investigation of the divergent, non-redundant activities of IFN{lambda}4 and other IFN{lambda}s. Contribution to the FieldViral infections remain major causes of death and disease in humans and other animals. Interferons (IFNs) are a diverse group of host signalling proteins that can induce a potent antiviral state in cells and are intimately involved in the outcome of infection. Genetic variants within one IFN (interferon lambda 4, IFN{lambda}4) are associated with the outcome of hepatitis C infection in humans. However, how IFN{lambda}4 functions - and how natural variants affect its activity - remains poorly understood. Comparing how the antiviral activity changes over time following stimulation with different IFN{lambda}s, we identified that IFN{lambda}4 induces a more rapid antiviral state compared to other IFN{lambda}s in liver and intestinal cells. Importantly, this response was conserved within human variants and between humans and non-human primates (chimpanzee and Rhesus macaque). Our results shed light on the unique functions of the divergent IFN{lambda}4 protein.

immunology↗

bioRxiv2021

ELICE16INDURES (R): a plant immune-priming activator targeting jasmonate metabolism via TIFY and RHOMBOID proteins in Hordeum vulgare

Priming activity of plant-based allelochemicals is advanced research nowadays meaning a high potential in sustainable agriculture. The ELICE16INDURES(R) (RIMPH LTD, Hungary) plant conditioner of CO2 botanical extracts is rich in plant-active ingredients such as phenolic compounds, alkaloids, and flavonoids formulated in small multilamellar liposomes. This product was investigated in autumn barley (Hordeum vulgare). Field experiments of ELICE16INDURES showed augmented NDVI values interconnected with higher photosynthetic activity and yield increase. Background of the better vitality of plants was investigated by whole genomic gene expression profiling and showed an enhanced response to wounding, jasmonic acid, oxidative detoxification, and chloroplast activity. Among top50 differentially expressed genes the TIFY domain protein TIFY11B and RHOMBOID-like protein 2 related to JA signaling were up-regulated in field-collected samples. Phytotron experiments of barley were set up to validate and evaluate the transcriptomic effect of ELICE16INDURES. Well-studied priming active agents such as salicylic acid and beta-aminobutyric acid were compared with ELICE16INDURES and confirmed as priming inducer material with positive regulation of TIFY11B, TIFY3B, TIFY9, TIF10A, and RHOMBOID like protein 2 by using NGS GEx and RT-qPCR methods. One-sentence summaryELICE16INDURES(R) is a plant conditioner agent with a high amount of allelochemicals encapsulated into small multilamellar liposomes and found as an immune priming activator tested in H. vulgare field and phytotron cultures.

plant biology↗

bioRxiv2021

Methylomic alteration in peripheral blood lymphocytes of prodromal stage and first-episode Chinese Han schizophrenia patients

BackgroundAlthough epigenetic dysregulation has long been proposed to promote the onset of schizophrenia, the landscape of the methylomic changes across the whole genome is yet established. MethodsUsing Infinium Human Methylation 850 BeadChip Array and MethylTarget sequencing method, we investigated the genome-wide methylation profiles and further validated methylation profiles of target genes in peripheral blood lymphocytes between individuals with psychosis risk syndrome (PRS), patients with first-episode schizophrenia (FES) and healthy controls (HC) in Chinese Han population. ResultsWe detected 372 sites between psychosis risk syndrome (PRS) and healthy controls (HC), which increased to 460 sites in first-episode schizophrenia (FES) with 207 sites shared. Both PRS and FES featured profound hypomethylation within gene body. Gene ontology and network annotation merged on loci enriched in disease associated signaling pathways (MAPK(Mitogen Activated Protein Kinases), Glutamatergic, GABAergic etc.). ConclusionsOur study implicated characteristic hypomethylation in both the discovery and validation cohorts in SYNGAP1, one of the frequently studied genes in neurodevelopmental disorders. This is the first methylome-wide association study between PRS and FES in Chinese Han population. Our findings provide potential biomarkers that can be used for future development of disease therapy and management.

genetics↗

bioRxiv2020

rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins

RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs can deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/296160v2_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@7a2dc6org.highwire.dtl.DTLVardef@1533c0dorg.highwire.dtl.DTLVardef@18bb4a1org.highwire.dtl.DTLVardef@ffe601_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2020

Glioblastoma Cell Migration is Directed by Electrical Signals

BackgroundElectric field (EF) directed cell migration (electrotaxis) is known to occur in glioblastoma multiforme (GBM) and neural stem cells, with key signaling pathways frequently dysregulated in GBM. One such pathway is EGFR/PI3K/Akt, which is down-regulated by peroxisome proliferator activated receptor gamma (PPAR{gamma}) agonists. We investigated the effect of electric fields on GBM differentiated and stem cell migration and whether this was affected by treatment with the PPAR{gamma} agonist pioglitazone. MethodsPrimary GBM cell lines were cultured as differentiated and glioma stem cells (GSCs) and then exposed to EFs using electrotaxis chambers and imaged with time lapse microscopy. Cells were then treated with varying concentrations of pioglitazone and/or its inhibitor GW9662 and their responses to EFs examined. ResultsWe demonstrated that GBM differentiated and GSCs have opposing preferences for anodal and cathodal migration, respectively. Pioglitazone treatment resulted in significantly decreased directed cell migration in both cell types. Western blot analysis did not demonstrate any change in PPAR{gamma} expression with and without exposure to EF. ConclusionsOpposing EF responses in primary GBM differentiated cells and GSCs can be inhibited chemically by pioglitazone, implicating GBM EF modulation as a potential target in preventing tumour recurrence.

cancer biology↗

bioRxiv2020

Determination of primary microRNA processing in clinicalsamples by targeted pri-miR-sequencing

MicroRNA expression is important for gene regulation and deregulated microRNA expression is often observed in disease such as cancer. The processing of primary microRNA transcripts is an important regulatory step in microRNA biogenesis. Due to low expression level and association with chromatin primary microRNAs are challenging to study in clinical samples where input material is limited. Here, we present a high-sensitivity targeted method to determine processing efficiency of several hundred primary microRNAs from total RNA using as little as 500 thousand Illumina HiSeq sequencing reads. We validate the method using RNA from HeLa cells and show the applicability to clinical samples by analyzing RNA from normal liver and hepatocellular carcinoma. We identify 24 primary microRNAs with significant changes in processing efficiency from normal liver to hepatocellular carcinoma, among those the highly expressed miRNA-122 and miRNA-21, demonstrating that differential processing of primary microRNAs is occurring and could be involved in disease. With our method presented here we provide means to study pri-miRNA processing in disease from clinical samples.

molecular biology↗

bioRxiv2018

Phase Separations Driven by RNA Scaffolds and Protein Sequestration in FXTAS

Recent evidence indicates that specific RNAs promote formation of ribonucleoprotein condensates by acting as scaffolds for RNA-binding proteins (RBPs).\n\nWe systematically investigated RNA-RBP interaction networks to understand ribonucleoprotein assembly. We found that highly-contacted RNAs are highly structured, have long untranslated regions (UTRs) and contain nucleotide repeat expansions. Among the RNAs with such properties, we identified the FMR1 3 UTR that harbors CGG expansions implicated in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).\n\nWe studied FMR1 binding partners in silico and in vitro and prioritized the splicing regulator TRA2A for further characterization. In a FXTAS cellular model we validated TRA2A-FRM1 interaction and investigated implications of its sequestration at both transcriptomic and post-transcriptomic levels. We found that TRA2A co-aggregates with FMR1 in a FXTAS mouse model and in post mortem human samples.\n\nOur integrative study identifies key components of ribonucleoprotein aggregates, providing links to neurodegenerative disease and allowing the discovery of new therapeutic targets.

molecular biology↗