Biology subjects

Hou, X.

Publications and source records attributed to Hou, X..

At least 19 recordsLinked to original sources

bioRxiv2026

Brain state locks silent memories in a trained fly connectome

Complete connectomes now exist for insect nervous systems, but whether a fixed wiring diagram can learn, and what its memories consist of, is unknown. Here, we trained a spiking model of the whole male Drosophila central nervous system, 167,106 neurons with fixed wiring, to plan moves and to remember a visual cue. Spikes write the cue into neuronal adaptation, which holds it silently until the next input reads it out. Cells that hold the trace are enriched for transcripts of a calcium-activated potassium channel in fly cell atlases. The learned readout recalls the trace only in the brain state of learning: the same trace evokes a different response at another delay, and a disease-like loss of potassium current rewrites the trace and changes how it is read. Learning in the new state is spared. Memory failure can arise from a change of state rather than a loss of storage.

neuroscience↗

bioRxiv2026

Analysis of genome sequences of marine isolates of Saccharomyces cerevisiae

Saccharomyces cerevisiae is the workhorse of the fermentation industry, as well as a dominant laboratory model organism and chassis for synthetic biology. The great majority of known isolates are from terrestrial sources, but a number of strains are reported to have been isolated from seawater and marine sediments and organisms. Marine strains may have superior tolerance to salt and fermentation inhibitors, and other properties which may be useful in industry, especially in processes based on seawater and marine biomass, as well as casting new light on the physiology and evolution of this species. We have recently reported the isolation of several marine strains of S. cerevisiae and comparisons with terrestrial strains for ethanol production. Here we describe the genome sequences of three marine S. cerevisiae strains, AZ65, AZ118 and AZ123. To the best of our knowledge, these are the first genome sequences of marine S. cerevisiae strains for which published isolation data are available. Superior salt and inhibitor tolerance of the strains, compared to multiple terrestrial and industrial comparators, was confirmed. Analysis of the ENA locus, believed to be related to salt tolerance in S. cerevisiae, did not show strong evidence for modification of copy number, protein sequence, or promoter sequence of this locus in response to a marine habitat. The physiological and genetic basis of salt and inhibitor tolerance thus remains to be determined.

microbiology↗

bioRxiv2026

Structural streamlining of axonemal doublet microtubules in Plasmodium male gametes

Male gametogenesis in malaria parasites produces up to eight flagellated gametes within approximately 15 min, requiring de novo construction of motile axonemes on an unusually short timescale. Here we combine cellular cryo-electron tomography, high-resolution cryo-EM, proteomics, and parasite genetics to define the molecular architecture and assembly states of the Plasmodium male gamete axoneme. The doublet microtubules retain the principal surface-associated motility modules but contain a markedly reduced luminal microtubule inner protein network. Their inner junction lacks PACRG and is instead organized by CFAP20 and CFAP52, whose combined loss disrupts doublet integrity and exflagellation. We further identify a calmodulin protein at the outer dynein arm docking region and show that outer dynein arms accumulate progressively during gametogenesis. These findings establish distinct form of axonemal remodeling in Plasmodium and reveal the ordered assembly of structural and motor modules during rapid male gamete formation.

cell biology↗

bioRxiv2026

Multi-kingdom microbial diversity and interaction landscapes in mosquitoes revealed by 5,163 individual meta-transcriptomes

Mosquitoes are pathogen vectors embedded within diverse microbial ecosystems. However, the nature and interactions among their multi-kingdom microbiome remain poorly understood. We conducted a nationwide single-mosquito meta-transcriptomic survey of 5,163 mosquitoes representing 100 species across China, integrating viral discovery with marker-gene profiling of bacteria, archaea, fungi, and other eukaryotic microbes. From this, we identified 1,606 microbial species-level taxa, including extensive novel diversity, and revealed pronounced host species-specific organization of mosquito-associated communities. We detected 34 pathogens or potential pathogens of human or animal relevance, whose prevalence, abundance, host range, and geographic distribution defined distinct epidemiological patterns. Network analysis uncovered pervasive cross-kingdom microbial associations, including candidate antiviral relationships involving Wolbachia and other microbial taxa. Our study establishes a detailed view of the full-spectrum microbiome and provides a resource and conceptual framework for studying vector competence, pathogen emergence, and microbiome-informed mosquito-borne disease control.

microbiology↗

bioRxiv2026

Nuclear Cathepsin L Remodels the Replication Machinery to Create a Therapeutic Vulnerability in Ovarian Cancer

Abstract Therapeutic resistance in ovarian cancer is frequently driven by persistent replication stress, yet the molecular mechanisms that convert replication stress into a therapeutically exploitable vulnerability remain incompletely understood. Here, we identify drug-induced nuclear cathepsin L (nCTSL) as a previously unrecognized regulator of replication stress and DNA repair. Clofarabine (CLF) combined with the ATR inhibitor AZD6738, or the CHK1 inhibitor prexasertib promoted nuclear accumulation of CTSL, where it remodeled the replication machinery through degradation of CCNE1, MCM3, MCM6, and geminin, accompanied by loss of RAD51 and 53BP1 and increased {gamma}H2AX and phospho-RPA2. DNA fiber analysis demonstrated marked inhibition of replication fork progression following CLF-based combinations, whereas CTSL depletion accelerated fork progression and abolished therapy-induced replication stress. Reconstitution with the nuclear M1F CTSL isoform restored replication restraint, confirming a direct role for nuclear CTSL in regulating replication dynamics. GFP-based DNA repair reporter assays further revealed that CLF-based combinations suppress DNA repair competence in a CTSL-dependent manner, indicating that nuclear CTSL couples replication stress amplification with functional inhibition of repair pathways. Functionally, CLF-based combinations selectively targeted transformed fallopian tube secretory epithelial cells while sparing non-transformed counterparts, demonstrated broad activity in patient-derived ovarian cancer ascites spheroids, and significantly inhibited tumor growth and prolonged survival in vivo. Collectively, our findings identify nuclear CTSL as a mechanistic driver of replication stress that remodels the replication machinery, impairs DNA repair, and creates a therapeutically exploitable vulnerability in ovarian cancer. We propose that nuclear CTSL promotes a transition from replication competence to replication catastrophe, thereby establishing a conceptual framework for biomarker-guided therapeutic strategies targeting CTSL-dependent replication stress.

cancer biology↗

bioRxiv2026

Refractive index modulation by ultraviolet absorption of canonical amino acids for in vivo optical transparency

The inherent opacity of most mammalian tissues limits deep-tissue optical imaging and light delivery. In contrast, the natural transparency of certain species and ocular tissues has been hypothesized to involve proteins with unusually high refractive indices. Here, we systematically analyze the ultraviolet absorption and visible-range refractive index modulation of canonical amino acids to identify key contributors to high-refractive index proteins. We identify arginine as a leading candidate, combining strong ultraviolet absorption, efficient refractive index modulation, physiological pH, and biocompatibility. These properties are validated through successful achievement of optical transparency in both ex vivo and in vivo tissues. Our findings establish a foundation for using abundant endogenous biomolecules to achieve in vivo tissue transparency and suggest a strategy for engineering proteins enriched in high-performing amino acids to enable efficient, biocompatible tissue clearing.

biophysics↗

bioRxiv2026

TEAD1 signaling modulates adrenal chromaffin maturation

Chromaffin cells synthesize and secrete catecholamines to coordinate systemic stress responses and regulate diverse neuroendocrine and metabolic functions. However, the molecular mechanisms governing chromaffin-cell differentiation and their disruption in pheochromocytoma (PC) remain incompletely understood. Here, through integrated analyses of human developmental atlases, patient-derived transcriptomic datasets, genetically engineered mouse models, and chromaffin organoids, we identify TEAD1 signaling as a critical regulator of chromaffin-cell differentiation and function. In vivo studies using a chromaffin cell-specific TEAD1 overexpression mouse model demonstrated that suppression of TEAD signaling markedly compromises chromaffin-cell differentiation and endocrine function. Additionally, compared with other TEAD family members, TEAD1 transcriptional activities are readily affected by sequences near the binding motif. To identify therapeutically actionable regulators of TEAD1 signaling, we established a TEAD activity-based screening platform and identified the serotonin receptor HTR5A antagonist SB699551 as a potent modulator of chromaffin-cell state. SB699551 suppressed PC-cell proliferation in vivo, and remodeled catecholamines synthesis in primary human PC cells. Additionally, application of SB699551 to human PC tumor revealed a subpopulation of primary chromaffin cells sensitive to this compound. Mechanistically, CXXC5 and L1CAM were identified as downstream SB699551-TEAD1 signaling effectors mediating chromaffin-cell proliferation and differentiation. Overall, we demonstrate that TEAD1 signaling is a fundamental mechanism regulating chromaffin cell differentiation and that modulation of TEAD1 signaling via SB699551 offers a new area of investigation in chromaffin cell biology.

molecular biology↗

bioRxiv2026

A generalizable speech neuroprosthesis

Intracortical brain-computer interfaces (BCIs) can restore communication to people with vocal tract paralysis by decoding cortical activity during attempted speech into text. State-of-the-art systems pairing neural-to-phoneme decoders with phoneme-to-word language models have achieved word error rates (WERs) as low as 1%, but only after collecting thousands of sentences of training data. Shortening the data collection process would facilitate scaling this new technology by reducing the time from device implant to high-accuracy communication. Here we introduce a transformer-based decoder model trained jointly across six intracortical speech BCI participants. For every participant -- regardless of sex, disease etiology, or attempted speaking strategy -- a multi-user model decoded speech more accurately (over 50% lower relative WER on average) than models trained on individual users data. Notably, the multi-user model could be finetuned on fewer than 200 sentences from a held-out user to achieve a WER below 7%. These results reveal how to pool intracortical data across people to yield more accurate, generalizable, and rapidly-deployable decoding models.

bioengineering↗

bioRxiv2026

Brain2voice 2.0: High-performance voice synthesis brain-computer interface

Brain-computer interfaces (BCIs) offer a promising solution to speech loss due to neurological injury by decoding intended speech directly from brain activity. While recent BCIs have restored high-accuracy text-based communication, they fail to provide instantaneous voice output essential for the natural flow of conversation. Brain-to-voice BCIs address this gap by decoding voice directly from neural signals. However, even the state-of-the-art (SOTA) BCI-synthesized voice is not yet intelligible enough for real-world adoption. We introduce brain2voice 2.0, a new multimodal Transformer-based BCI decoder architecture capable of synthesizing highly intelligible voice from intracortical neural signals in real-time. Brain2voice 2.0 is trained on continuous and custom-tokenized acoustic targets and phoneme targets, leveraging their complementary speech information. We use self-supervised and adversarial training objectives that enhance acoustic feature quality and improve synthesis intelligibility. At each 10 ms timestep, the model causally outputs continuous and tokenized acoustic features for real-time voice synthesis as well as time-aligned phoneme predictions (raw phoneme error rate: 7%, comparable to the latest brain-to-text models). We evaluated this new approach on our prior intracortical brain-to-voice benchmark dataset (Wairagkar et al. 2025). Naive human listeners transcribed brain2voice 2.0 synthesized voice with a word error rate of 5.24%--an 8x improvement in intelligibility over previous SOTA results (43.75%). Brain2voice 2.0 demonstrates that highly intelligible real-time voice synthesis from neural signals is achievable, for the first time crossing the intelligibility threshold necessary for clinically viable brain-to-voice BCIs for people with paralysis.

neuroscience↗

bioRxiv2026

The Par complex regulates apical-basal cell polarity through modulation of FAK signaling homeostasis

Cell polarity complexes are essential for embryogenesis, but their regulatory mechanisms during early developmental transitions remain incompletely understood. Here, we individually deleted the Crumbs, Par, and Scrib polarity complexes in mouse embryonic stem cells (mESCs). While loss of any single complex did not affect pluripotency or proliferation, deletion of Par complex disrupted the naive-to-primed transition and impaired subsequent differentiation, particularly lumen formation in neural tube organoids. Mechanistically, Par complex deficiency led to hyperphosphorylation of focal adhesion kinase (FAK) at the primed stage, driving a morphological shift from flat monolayer clusters to dome-shaped colonies. FAK inhibition rescued the aberrant morphology. Upstream, Par complex loss increased AKT phosphorylation, which remodeled extracellular matrix (ECM) and regulated integrin signaling via FURIN-LEFTY, ultimately modulating FAK activity. In addition, conditioned medium from wild-type cells partially rescued differentiation defects in Par knockout cells in a LEFTY-dependent manner. These phenotypes were consistently observed in naive-to-primed transition, neural stem cell differentiation, embryoid body formation, teratoma assays, and neural tube organoid differentiation. Together, these findings establish a Par complex-AKT-FURIN-LEFTY-ECM-integrin-FAK signaling cascade that links apical-basal polarity to early lineage specification and morphogenesis, providing a mechanistic framework for how polarity cues are translated into developmental outcomes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/722465v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@179e0adorg.highwire.dtl.DTLVardef@8d83bdorg.highwire.dtl.DTLVardef@c425fforg.highwire.dtl.DTLVardef@19a8ee5_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance StatementThis study elucidates the molecular mechanism by which the Par complex regulates the establishment of cell polarity. The authors demonstrate that the Par complex promotes the expression of the protein convertase FURIN via AKT signaling, thereby enhancing the maturation and secretion of LEFTY protein. This process remodels the ECM and modulates integrin signaling, ultimately regulating FAK activity and controlling the establishment of cell polarity. These findings reveal how polarity cues govern early lineage specification and morphogenesis, with implications across multiple developmental contexts.

developmental biology↗

bioRxiv2026

Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling

AbstractParkinsons disease (PD) is commonly associated with dysfunctional mitochondrial homeostasis. PINK1, a S/T kinase mutated in early-onset PD, generates phosphoserine 65 ubiquitin (pS65Ub) on damaged mitochondria facilitating their removal. Here, we show that pS65Ub translocates into the nucleus after generation at damaged mitochondria and is directly attached to substrates by resident E3 ligases. Histone H2A is a major substrate and is modified at lysine 119 (H2AK119) by the polycomb silencer, E3 ligase RING1B. At nucleosomes, pS65Ub simultaneously suppresses RING1B and potentiates H2A deubiquitinases USP16 and USP21. Epigenetic profiling and RNA sequencing reveal that pS65Ub is enriched at the promoters of poorly expressed yet dynamically regulated genes and is associated with H2AK119ub depletion. Functionally, we show that pS65Ub enrichment drives polycomb target gene expression, which accelerates the maturation of dopaminergic neurons. Importantly, post-mortem PD brains exhibit elevated nuclear pS65Ub, potentially linking nuclear pS65Ub accumulation with disease pathogenesis. Together, these data indicate that pS65Ub generated at damaged mitochondria regulates fundamental cellular processes at distant sites.

cell biology↗

bioRxiv2026

Tartrazine clears live cells while preserving viability at high refractive indices and osmolality

Tissue-clearing techniques have transformed optical imaging of fixed specimens, yet their application to living systems remains limited by toxicity and removal of key tissue components. We recently demonstrated that absorbing molecules such as tartrazine can reversibly render live mouse skin transparent. Subsequently, it was reported that isotonic protein solutions can achieve ex vivo and in vivo cellular clearing. However, discrepancies remain regarding the optimal refractive index (RI) for live-cell clearing and the impact of elevated osmolality on cell viability. Here, using cultured mammalian cells, we systematically examine the dependence of optical contrast on medium RI and the effects of hyperosmolality. We find that, contrary to the recent report of an optimal RI of 1.36[~]1.37 for suspended cells, densely-packed adherent cells exhibit a monotonic decrease in phase contrast up to an RI of 1.41 with tartrazine. Moreover, even under highly hyperosmotic conditions ([~]1200 mOsm/kg), cultured cells exhibit minimal deformation and negligible loss of viability for up to 30 min in the clearing solution. These results demonstrate that tartrazine enables effective live-cell clearing at RI up to 1.41 while preserving viability under elevated osmolality, and motivate future studies to define optimal conditions for in vivo optical clearing. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=44 SRC="FIGDIR/small/717314v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@1ec9fbforg.highwire.dtl.DTLVardef@1ebe9e6org.highwire.dtl.DTLVardef@1492c3corg.highwire.dtl.DTLVardef@f75559_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2026

IEKB: a comprehensive knowledge base for inner ear genetics integrating curated associations, cochlear interactions, Bayesian candidate prioritisation, explainable dark-gene support relations, and a scientific entity network

Inner-ear genetics has expanded rapidly, yet the supporting evidence remains dispersed across a vast literature and across resources that typically emphasise loci, variants, or expression data rather than integrated biological interpretation. Here we present the Inner Ear Knowledge Base (IEKB; https://earkb.org), an open database that unifies curated associations, cochlear interaction evidence, candidate prioritisation, explainable support relations, and network exploration for inner-ear research. IEKB was built with an automated agent-assisted curation workflow that combines schema-constrained literature extraction, continuous human monitoring, and final expert review by inner-ear genetics researchers. By systematically analysing 250,696 PubMed-indexed records retrieved across 16,563 screened genes, IEKB curates 6,051 gene-phenotype-disease associations from 2,494 genes across 43 phenotype categories and 4,102 cochlear gene-gene interactions with pathway, cell-type, and experimental context. IEKB further includes a Bayesian "dark matter" module that prioritises 243,071 candidate gene-phenotype associations for 13,229 genes across all 43 phenotypes (global AUC-ROC = 0.8603; global AUC-PR = 0.1674), together with a supervised dark-relation layer that ranks phenotype-specific known-gene support for each candidate and a multi-entity scientific network containing nearly 4,000 entities, 28,616 deterministic edges, and 83,712 literature-derived relational links. The web resource supports interactive search, multi-parameter filtering, gene-detail pages, bibliometric exploration, domain-specific enrichment against IEKB phenotype and disease gene sets, network visualisation, bulk download in CSV, JSON, SQLite, and XLSX formats, and natural-language evidence-grounded question answering through a companion conversational interface (IEKB QA). To our knowledge, IEKB is the first openly accessible inner-ear resource that integrates curated associations, cochlear interactions, probabilistic candidate prioritisation, auditable known-gene support relations for novel candidates, and a multi-entity scientific network within a single database. All data are released without registration under the CC BY 4.0 license.

bioinformatics↗

bioRxiv2026

Low-intensity vibration (LIV) cellular mechanotherapy reprograms tumor transcriptomes to suppress cancer-promoting inflammation

LIV is a non-pharmacological intervention for multiple pathologies, most notably pain, yet its potential in oncology remains unexplored due to poorly understood mechanotransduction pathways. Its therapeutic efficacy depends on precise dosing parameters - frequency, amplitude, and duration; suboptimal application, whether excessive or insufficient, risks exacerbating symptoms or rendering treatment ineffective. In a breast cancer-immune cell co-culture model, a 15-min regimen of 90-Hz, 0.43-g LIV attenuates protumorigenic crosstalk by suppressing proinflammatory cytokines and reprogramming malignant cells into a transient metastasis-incompetent "benignant" state that retains oncogenic markers but loses invasive capacity. Our results reveal LIV as a non-drug inhibitor of IFN{gamma} and CXCL12{beta} - silencing IFN{gamma} impairs inflammatory bursts, while silencing CXCL12{beta} starves the CXCR4/CXCR7 axis, depriving tumor cells of motility cues. LIV enforces a genome-wide transcriptional brake, upregulating tumor-suppressive miRNAs (hsa-miR-141, hsa-miR-122) while downregulating protumorigenic miRNAs (hsa-miR-105-5p, hsa-miR-181a-5p). This work repositions LIV as a non-drug modality for coordinately targeting multiple cancer hallmarks. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/716739v1_ufig1.gif" ALT="Figure 1"> View larger version (80K): org.highwire.dtl.DTLVardef@1100863org.highwire.dtl.DTLVardef@196bcf4org.highwire.dtl.DTLVardef@14f3903org.highwire.dtl.DTLVardef@2802fd_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_ST_ABSDosing PrecisionC_ST_ABSLIV mechanotherapy has an optimal therapeutic window. Too little is ineffective, while too much can exacerbate symptoms. This mirrors the pharmacokinetic language of classical pharmacology. The "Benignant" ConceptA 15-min regimen of 90-Hz, 0.43-g LIV attenuates protumorigenic crosstalk by suppressing proinflammatory cytokines and reprogramming malignant cells into a transient, metastasis-incompetent benignant state defined by mechanical constraint rather than pharmacological intervention. Dual Cytokine SilencingLIV acts as a non-pharmaco-logical inhibitor of IFN{gamma} and CXCL12{beta}. IFN{gamma} is a double-edged sword in cancer (pro-immunity vs. exhaustion), and CXCL12{beta} is the specific isoform implicated in metastasis. Targeting both simultaneously addresses immune crosstalk and chemotaxis. In briefMeena et al. demonstrate that the efficacy of LIV hinges on optimal dosing parameters. When applied correctly, it functions as a non-drug modality to target multiple oncogenic and inflammatory pathways. At the molecular level, LIV drives global transcriptional repression via miRNA regulation, increasing tumor-suppressive miRNAs (hsa-miR-141, hsa-miR-122) and decreasing protumorigenic miRNAs (hsa-miR-105-5p, hsa-miR-181a-5p).

cancer biology↗

bioRxiv2026

Identification of a somatic H3K23me3 methyltransferase SET-19 in C. elegans

Histone methylation plays essential roles in modulating chromatin organization and gene expression. H3K23 methylation is a conserved histone modification, yet its biological roles and the enzymes responsible for its deposition remain poorly understood. Here, we show that the loss of set-19 leads to a pronounced reduction in H3K23 methylation in C. elegans, as revealed by quantitative mass spectrometry, western blotting, and immunofluorescence staining. In vitro biochemical assays show that recombinant SET-19 proteins purified from E. coli directly catalyze H3K23 methylation. Genome-wide chromatin immunoprecipitation assays reveal that H3K23me3 is enriched at heterochromatic regions and that loss of set-19 alters H3K23me3 levels, accompanied by derepression of gene expression. Genetic analyses indicate that SET-19 is dispensable for both germline and somatic RNAi as well as transgenerational epigenetic inheritance of RNAi. SET-19 is predominantly expressed in somatic cells and specifically mediates H3K23me3 deposition in somatic tissues. The loss of set-19 causes a developmental delay without affecting fertility. Together, our results identify SET-19 as a somatic H3K23 methyltransferase and link H3K23me3 to gene repression in C. elegans.

genetics↗

bioRxiv2026

Cambrian Artiopoda Reveals a Constraint in Euarthropod Brain Evolution

Cambrian stem mandibulates and chelicerates have provided robust evidence of brains that conform to a cerebral ground pattern also defining extant euarthopods. But information about the brains of trilobites or their immediate relatives remains a mystery. Here we describe the detailed organization of the specialized brain of Xandarella spectaculum, a member of the subphylum Trilobitomorpha which went extinct at the end Permian. While retaining the pre-Cambrian cephalic ground pattern as three seriate domains, empirical evidence indicates clade-specific accentuation of some and loss of other neural arrangements typifying extant mandibulates. The trilobitomorph deutocerebral organization is dominated by exaggerated glomerular centers whereas its prominent lateral eyes supply minute visual centers. Paired ocelli are associated with the prominent prosocerebral bridge of the forebrain, an essential center for path integration. Together these modifications indicate neural organization typifying some extant benthic crustaceans and even hexapods that engage in foraging behaviors. With reference to existing neurological attributes of living pancrustaceans major divergences of the trilobitomorph brain from the ancestral cerebral ground pattern may have weakened its resilience to geo-ecological disruptions and hence the final extinction of the clade to which trilobitomorphs belong.

evolutionary biology↗

bioRxiv2026

RdRpCATCH: A unified resource for RNA virus discovery using viral RNA-dependent RNA polymerase profile Hidden Markov models

Recent advances in large-scale sequence mining have expanded our knowledge of RNA virus diversity. Most genome mining approaches for detecting RNA viruses that encode RNA-dependent RNA polymerase (RdRp) rely on identifying this conserved protein by employing profile Hidden Markov Models (pHMMs) to scan sequencing datasets. Recently, several new pHMM databases for RdRp detection have been released, each following distinct design principles. However, their relative performance is unclear and their accessibility to users without specialized computational expertise is limited. Here, we introduce the RdRp Collaborative Analysis Tool with Collections of pHMMs (RdRpCATCH: https://github.com/dimitris-karapliafis/RdRpCATCH), developed to consolidate publicly available RdRp pHMM resources into a single, accessible platform. RdRpCATCH enables the scanning of (meta)transcriptomic assemblies to discover RNA viruses and provides subsequent taxonomic annotation of detected contigs. A comparative analysis of RdRp pHMM databases reveals that most are highly effective at detecting known diversity of RNA viruses while minimizing false positives, supporting their joint use within RdRpCATCH. RdRpCATCH is distributed as both a conda package and a web server application (https://rdrpcatch.bioinformatics.nl), facilitating access for researchers with diverse expertise. By integrating multiple pHMM resources, this unified framework addresses fragmentation in the field and reduces technical barriers, enabling comprehensive viral discovery.

bioinformatics↗

bioRxiv2026

A dual-factor complex governs archaeal ribosome hibernation by sensing energy status

Efficient coupling of cellular energy status to ribosome regulation is fundamental for cellular survival. Here, we identify the Archaeal Ribosome regulatory Complex (ARC)--a previously uncharacterized dual-factor complex comprising ARC-P and ARC-A. Cryo-EM reveals that ARC anchors to the small ribosomal subunit, establishing a stringent blockade of the tRNA and mRNA paths via an electrostatic wedge mechanism. This hibernation state is modulated by energy status: the complex remains stably associated under low-energy conditions, whereas ATP binding triggers rapid mobilization. Genetic analyses demonstrate that ARC acts as a translational brake essential for preserving ribosomal structural integrity, with ARC-A serving as the primary inhibitory factor. Notably, while the loss of ARC accelerates growth, it impairs recovery in proportion to stress severity. Phylogenomic analysis identifies ARC as an evolutionarily novel and widely distributed dual-factor system, revealing a conserved regulatory strategy for metabolic-translational coupling across diverse archaea. Our findings define a fundamental strategy where modular complexes integrate metabolic sensing with mechanical sequestration to balance growth and persistence.

biochemistry↗