Biology subjects

Wei, G.

Publications and source records attributed to Wei, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Mathematical AI Predicts 40% and 57% Influenza Vaccine Effectiveness Against H1N1 and H3N2, Respectively, for the 2026--2027 U.S. Season

Background: Clinical influenza vaccine effectiveness (VE) has often been low over the past two decades, highlighting the need for preseason VE forecasting. Timely forecasts could help health authorities plan prevention strategies and allocate healthcare resources. However, preseason forecasting of clinical influenza VE remains relatively uncommon. Methods: We obtained hemagglutinin (HA) sequences from GISAID for U.S. specimens collected in August--September before each influenza season from 2010--2011 through 2024--2025. After quality screening, we compared each virus with the corresponding vaccine target strain for the same season and subtype or lineage using two mathematical distances based on amino acid patterns in the HA protein. We calculated mean distances for each season and subtype or lineage and paired them with published clinical VE estimates, yielding 26 observations across 13 seasons. Using a mathematical AI approach, we fitted linear regression models of VE against each distance and evaluated their predictive performance by forecasting later seasons using data from earlier seasons, with the historical mean VE for each subtype or lineage as a reference. We then applied the same approach to 87 HA sequences collected in August--September 2026 to forecast VE for the 2026--2027 season. Results: We generated component-specific forecasts of influenza VE for the upcoming 2026--2027 U.S. season. Both mathematical distances were negatively associated with historical VE, indicating that greater differences between circulating viruses and vaccine strains were associated with lower VE. The topological model forecast VE of 40.3%, 56.9%, and 47.1% against A(H1N1)pdm09, A(H3N2), and B/Victoria, respectively, whereas the geometric model forecast corresponding VE values of 34.0%, 56.8%, and 51.1%.

bioinformatics↗

bioRxiv2026

A contact-mediated transfer mechanism directs in cis localization and spread of Xist RNA

X chromosome inactivation in mammals is driven by the long non-coding RNA Xist, which localizes and spreads across the chromosome from which it is transcribed. Although several factors required for Xist localization have been identified, the underlying mechanism remains unclear. Here, we combine Nuclear-BRITE, a method for visualizing and quantifying the dynamics of individual Xist RNA molecules, with acute depletion of key localization factors. We find that Xist molecules remain constrained throughout interphase, consistent with continuous association with chromatin. Building on this observation, we identify a contact-mediated transfer mechanism in which 3D chromosome dynamics promote handover of Xist molecules between chromosomal sites. We further show that the Xist-binding proteins SPEN and HNRNPU play distinct roles in this process by promoting Xist - Xist and Xist - chromatin interactions, respectively. Together, our findings define a mechanism for Xist RNA spreading and provide a framework for understanding its unique chromosome-wide localization.

molecular biology↗

bioRxiv2026

Stomatal Complex Ionomes Explain Divergent Gas Exchange Responses to Salinity in Maize and Faba Bean

Salinity tolerance is commonly associated with whole leaf Na exclusion and maintenance of K homeostasis, but whether spatial ion partitioning among functional leaf compartments contributes to stress adaptation remains unclear. Here, we investigated the relationship between bulk leaf and stomatal complex ionomes and gas exchange performance under salinity using two contrasting genotypes in both maize and faba bean crops. Maize generally maintained higher photosynthesis and stomatal conductance than faba bean under salt stress, which was associated with lower Na accumulation, stronger K retention and distinct ion partitioning patterns between bulk leaf tissue and the stomatal complex. Enrichment analysis revealed that stomatal complex ion composition provided information beyond bulk leaf ion concentrations, with Na and Cl- showing distinct distribution patterns associated with photosynthetic performance. Integrating physiological and ionomic traits further demonstrated that stomatal-complex ion traits captured additional variation in salinity responses. These findings identify the stomatal complex as a functionally distinct ionomic compartment and reveal compartment-specific ion partitioning as an important mechanism underlying species-specific salinity tolerance.

plant biology↗

bioRxiv2026

Guard Cell Chloroplast Remodeling Under Salt Stress Correlates with Ion Enrichment in Faba Bean

Salinity stress alters cellular ion homeostasis and photosynthetic activity, yet how guard cell chloroplast architecture contributes to salt adaptation remains poorly understood. Here, we investigated salt-induced chloroplast remodeling in guard cells of two faba bean genotypes, Fuego and Scoop, by integrating 3D chloroplast imaging, ion enrichment analysis and photosynthetic measurements. Salt stress induced distinct genotype-dependent changes in chloroplast morphology, with Fuego exhibiting pronounced chloroplast enlargement and reduced surface area-to-volume ratios under Na2SO and high NaCl, whereas Scoop showed treatment-dependent remodeling with larger chloroplasts under low NaCl and higher surface area-to-volume ratios under Na2SO and CaCl2. These structural responses were associated with differential Na and Cl partitioning at the stomatal complex surface. In Fuego, chloroplast size was negatively associated with photosynthetic rate, whereas Scoop showed positive relationships between chloroplast size and photosynthetic performance. Multivariate analysis further revealed coordinated associations among chloroplast architecture, ion enrichment and photosynthesis that distinguished the two genotypes under salinity. Our findings demonstrate that guard cell chloroplast remodeling is closely associated with genotype-specific salt responses and local ion partitioning. Integrating organelle structural plasticity with local ion homeostasis provides a spatially resolved perspective on the cellular basis of genotype-dependent salinity adaptation.

plant biology↗

bioRxiv2026

Neryl diphosphate-derived monoterpene biosynthesis via a biosynthetic gene cluster in the liverwort Marchantia polymorpha

Monoterpenes (C10) are a large group of specialized metabolites important for plant interactions with the environment. Their biosynthesis is well understood in seed plants, where geranyl diphosphate serves as the canonical substrate, but knowledge of monoterpene biosynthesis outside seed plants remains very limited. Here, we report neryl diphosphate (NPP)-derived monoterpene biosynthesis via a biosynthetic gene cluster in the liverwort Marchantia polymorpha. MpMTPSL2, a microbial-type terpene synthase, converts NPP into -phellandrene and D-limonene in vitro. CRISPR knockout lines showed reduced production of both monoterpenes, providing direct genetic evidence for its in planta function. MpCPT5, a cis-prenyltransferase (CPT) family member identified through co-expression with MpMTPSL2, was confirmed to encode NPP synthase, as its knockout plants abolished -phellandrene and D-limonene production. Subcellular localization analyses in protoplasts and stable transgenic plants demonstrated that both MpCPT5 and MpMTPSL2 localize to plastids, co-localizing across all cell types with markedly stronger signals in non-green plastids of oil-body cells. Consistent with this, expression of both genes under their respective promoters was nearly abolished in oil-body-deficient mutants and strongly upregulated in a gain-of-function line for oil-body formation. MpMTPSL2 and MpCPT5 are physically linked through a shared bidirectional promoter that drives their coexpression specific to oil body cells, forming a unique biosynthetic gene cluster whose coordinated expression is maintained by PRC2-mediated H3K27me3 repression. Phylogenetic analysis implies that NPP synthases in M. polymorpha and in flowering plants evolved independently from their respective long-chain CPT ancestors. These findings provide new insights into the mechanisms and evolution of monoterpene biosynthesis in non-seed plants. Significance statementMonoterpenes are a diverse group of specialized metabolites produced widely among land plants, yet our understanding of their biosynthesis outside seed plants remains limited. Here we report that in the liverwort Marchantia polymorpha, the non-canonical substrate neryl diphosphate is used for monoterpene biosynthesis. The functions of the monoterpene synthase gene MpMTPSL2 and the neryl diphosphate synthase gene MpCPT5 were demonstrated through CRISPR knockouts. These two genes are physically linked and share a bidirectional promoter. Promoter assays show both genes function in plastids within oil-body cells, revealing cell-type specificity. These findings shew new light on the mechanisms and evolution of monoterpene biosynthesis in non-seed plants.

plant biology↗

bioRxiv2026

Dynorphinergic neuroadaptations in the islands of Calleja: implications for alcohol use disorder

Dysregulation of the dynorphin (DYN) / kappa-opioid receptor (KOR) system is heavily implicated in symptoms of alcohol use disorder (AUD) including negative affective-like states that can drive maladaptive behavioral regulation. Substantial efforts have been made towards understanding the neurobiology of DYN / KOR dysregulation; however, the role of dynorphinergic islands of Calleja within the ventral striatum remain poorly understood. Presently, adult male Wistar rats were trained to self-administer 10% alcohol, exposed to either air or alcohol vapor for eight weeks, and alcohol self-administration and 22-kHz ultrasonic vocalizations (USVs) assessed during acute withdrawal. Subsequently, brains were extracted during acute withdrawal and DYN A-like immunoreactivity was measured in the ventral striatum. Alcohol vapor-exposed rats demonstrated increased alcohol consumption and 22-kHz USVs compared to air-exposed controls. Vapor-exposed rats additionally demonstrated increased DYN A-like immunoreactivity in the islands of Calleja. Moreover, the average DYN A neuron size positively correlated with the number of 22-kHz USVs in vapor exposed animals, but not in air-exposed controls. The present findings identify the islands of Calleja as a novel DYN-associated region that may be recruited during alcohol dependence with enhanced DYN plasticity in the islands of Calleja contributing to affective dysregulation in AUD and other neuropsychiatric conditions.

neuroscience↗

bioRxiv2026

A key role for chromosome compartment interactions in directing Xist RNA localisation

X-chromosome inactivation, the mechanism for dosage compensation in mammals, is orchestrated by the long non-coding RNA Xist which localises across the X chromosome in cis. The basis for in cis localisation remains poorly understood. To investigate in situ Xist localisation, we established MCPH1-deficient cell models that retain compacted interphase chromosomes, enabling visualisation of individualised chromosome territories. We find that Xist RNA is directed to sites around the periphery of compacted chromosome territories, and moreover that these sites correlate closely with A1-sub-compartments on the X chromosome. We further show that peripheral positioning of A1-sub-compartments occurs on all chromosomes and is a hallmark of early prophase. A key role for compartment interactions in Xist localisation is further supported by analysis of MCPH1-deficient models where Xist is overexpressed (from the X chromosome or an autosomal Xist transgene), and following depletion of HNRNPU, a key factor that anchors Xist RNA to chromosome territories.

genetics↗

bioRxiv2026

BioGAIP: A Scalable, User-Friendly and Robust LLM-Powered Multi-Agent System for Automated Bioinformatics Tasks

The rapid explosion of large-scale, high-throughput biological data has created an urgent demand for efficient analysis pipelines. Traditional bioinformatics approaches, while powerful, often require specialized computational expertise, placing them out of reach for bench biologists. Large Language Models (LLMs) offer new possibilities for automating complex reasoning and tool integration, yet existing LLM-based solutions have not sufficiently lowered this barrier, and expert-level analysis remains inaccessible to most nonexperts. Here, we present BioGAIP, an LLM-powered agent that integrates expert-level reasoning within an end-to-end platform for bioinformatics tasks. By coupling optimized autonomous agents with full graphical interfaces, BioGAIP transforms complex analytical workflows into an automated, user-friendly, and low-intervention process with natural language input. Key features of BioGAIP include dynamic information retrieval, automatic environment configuration, and self-directed design of analysis pipelines, making large-scale multi-omics analysis highly accessible. Built on agent-based client-server architecture, BioGAIP ensures secure resource management and supports heavy computational demands. Extensive evaluations on diverse published datasets demonstrate that BioGAIP reliably recapitulates established biological insights and shows strong potential for novel discovery. By democratizing complex bioinformatics workflows, BioGAIP accelerates accessible data-driven discovery for both experts and nonexperts.

bioinformatics↗

bioRxiv2026

From external-input sensitivity to resident persistence: community assembly in a sink p-trap model

Microbial habitats that receive repeated external input may not remain shaped by that input forever if local retention allows resident communities to build up over time. Here, we used a controlled bench-scale sink p-trap system to examine how community assembly unfolded during initial establishment in new, bleach-treated p-traps. Two p-traps received repeated handwashing-water input, while one received tap water as baseline. The treated p-traps, but not the control, showed clear successional change toward later resident-like states. Nested-model comparisons further showed that recent external input had its greatest influence early in succession, but the p-traps own prior state remained the stronger predictor throughout. Final-day post-flush trajectories indicated short-term displacement from pre-flush positions, with later time points tending to move back toward late-stage resident centroids. Together, these results show that repeated inoculation does not necessarily keep communities under continued outside influence. Instead, retentive microbial habitats can shift over time from early sensitivity to external input toward persistence shaped more by local history.

ecology↗

bioRxiv2026

A Divergent Class of Arylamine N-Acetyltransferases Catalyzes Convergent Amidative Condensation of Polyketides in Manumycins Biosynthesis

Polyketides are prized for their structural complexity and therapeutic potential, yet the incorporation of amide bonds into their frameworks typically relies on linear, nonribosomal peptide synthetase (NRPS)-dependent assembly. The direct, convergent coupling of distinct polyketide chains via amide bond formation--an ideal strategy for combinatorial biosynthesis--has remained largely elusive. Here, we report the discovery of a novel family of arylamine N-acetyltransferases (NATs) from manumycin-type biosynthetic pathways that catalyze an unprecedented intermolecular amidative chain transfer/condensation between an acyl carrier protein (ACP)-tethered polyketide donor and a free polyketide acceptor. Biochemical, structural, and molecular dynamics studies reveal that the representative enzyme, ColC2, possesses a distinctive substrate-binding pocket that diverges from canonical arylamine NATs, conferring exceptional promiscuity toward diverse acyl donors and acceptors. We demonstrate the utility of this biocatalyst by coupling arylamines with either synthetic acyl-thioesters or polyketide synthase (PKS) machinery to generate a library of non-natural polyketide amides and manumycin derivatives. These findings establish a new paradigm for amide bond formation in polyketide biosynthesis and position arylamine NATs as powerful tools for the development of novel therapeutics through combinatorial synthesis.

synthetic biology↗

bioRxiv2026

Microbiome depletion rejuvenates the aging brain

Aging is associated with cognitive decline and increased vulnerability to neurodegeneration driven by an array of molecular and cellular changes like impaired vascular integrity, demyelination, reduced neurogenesis, and chronic inflammation. Recent studies implicate the gut microbiome as a modulator of brain aging, but the underlying mechanisms remain elusive. Here, we show that depleting the gut microbiome by administering antibiotics to aged mice induces widespread molecular and structural rejuvenation in the brain. Our transcriptomic analyses by single-nucleus RNA sequencing revealed pronounced transcriptional shifts across multiple brain cell types. We confirmed that antibiotic treatment improves vascular density, promotes myelination, enhances neurogenesis, and reduces microglial reactivity. Functionally, microbiome-depleted mice showed improved hippocampal memory performance. Analyses of brain and plasma cytokine levels showed a decrease in several pro-inflammatory factors post-treatment and identified candidate factors, including the chemokine eotaxin-1. Inhibiting eotaxin-1 alone can reverse several aspects of brain aging. Our findings demonstrate that age-associated microbial inflammation contributes to brain aging and that its attenuation can restore youthful features at the molecular, cellular, and functional levels. Targeting the gut microbiome or its circulating mediators may therefore represent a non-invasive approach to promote brain health and cognitive resilience in aging.

neuroscience↗

bioRxiv2026

Dynamic Compression Flows for Neuroscience Data

While neuroscience experiments have repeatedly demonstrated the involvement of large populations of neurons in even simple behaviors, these studies have just as often reported that the collective dynamics of neural activity are approximately low-dimensional. As a result, methods for identifying low-dimensional latent representations of time series data have become increasingly prominent in neuroscience. However, most existing methods either ignore temporal structure or model time evolution using latent dynamical systems approaches. In the first case, dynamics may be distorted or even scrambled in the latent space, while in the second, many possible latent dynamics may give rise to the same data. Here, we address these challenges using a novel flow-matching approach in which data are generated by a pair of flow fields, one governing time evolution, the other a mapping between data and a low-dimensional latent space. Importantly, the dimension-reducing flow is trained to minimize distortions of the temporal dynamics, learning an identifiable low-dimensional representation that preserves temporal relations in the original data. Additionally, we constrain our latent spaces to have low-dimensional support in a soft, parameterized manner, taking inspiration from ideas on nested dropout. Across both neural and behavioral data, we show that this dual flow approach produces both more interpretable dynamics and higher-quality reconstructions than competing models, including in noise-dominated data sets where conventional approaches fail.

neuroscience↗

bioRxiv2025

RoBep: A Region-Oriented Deep Learning Model for B-Cell Epitope Prediction

MotivationAccurate in silico identification of B-cell epitope residues is crucial for antibody design and structure-guided vaccine development. Although recent protein language models and structure-aware methods can capture spatial information of tertiary structure when generating residue embeddings, most existing epitope predictors use these embeddings to perform classification for individual residues one by one, without enforcing spatial continuity for reported epitope residues. Such methods often result in biologically implausible predictions because B-cell epitope residues always cluster together on the antigen surface. ResultsWe present RoBep, a region-oriented B-cell epitope predictor that explicitly models the spatial clustering of epitope residues. RoBep introduces a novel region constraint mechanism and combines the advanced protein language model ESM-Cambrian with an equivariant graph neural network. Our method outperforms existing structure-based methods on the benchmark dataset, demonstrating improvements of 26%, 45%, 13%, and 43% in F1, MCC, AUPR, and AUROC0.1, respectively. In addition to residue-level predictions, RoBep can also provide antibody-antigen binding regions. Importantly, the predicted epitope residues are ensured to be spatially compact, enhancing biological plausibility and practical relevance for immunotherapeutic design. AvailabilityA user-friendly website for using RoBep is provided at https://huggingface.co/spaces/NielTT/RoBep. All datasets, source code used in this work, and implementation instructions of the website are publicly available at https://github.com/YitaoXU/RoBep.

bioinformatics↗

bioRxiv2025

Erucamide regulates retinal neurovascular crosstalk

Neurovasculoglial crosstalk is critical in establishing and maintaining a functional neurovascular unit. Breakdown in the unit is central to many neurodegenerative disorders of the CNS of which the retina is a component. A growing literature indicated that primary fatty acid amides (PFAMs) can regulate this crosstalk between vasculature and neuronal tissues. In this study we describe a central role for erucamide, a 22:1 mono-unsaturated omega-9 fatty acid amide, in degenerating retinal tissues. Using high-resolution global mass spectrometry-based metabolomics, we cataloged metabolites in murine models of retinal degeneration and show that while PFAMs, in general, are highly dysregulated, erucamide is the one most significantly diminished during photoreceptor atrophy. Using rodent models of retinal degeneration and novel organosilane-modified porous silicon nanoparticles (pSiNPs) for the in vivo delivery of erucamide, we demonstrate that erucamide activates CD11b+ myeloid cells, leading to the upregulation of angiogenic and neurotrophic cytokines that stabilize retinal degeneration. We identified TMEM19 as a novel binding protein for erucamide that is crucial for human iPSC-derived macrophage precursor cells activation and subsequent neurotrophic and angiogenic factor production. These findings reveal a previously unknown PFAM pathway that is modulated during retinal degenerative diseases, demonstrating that erucamide or functional analogues and their action through TMEM19 may be useful as a therapeutic alternative to neuroprotective and stem cell-based approaches for the treatment of retinal degenerative diseases.

neuroscience↗

bioRxiv2025

Optimized CRISPR Perturbation Illuminates the Functions of RNA Modification Proteins

iMAP is a large-scale CRISPR perturbation platform based on a germline-transmitted transgene comprising individually floxed, tandemly linked guides that can be inducibly expressed via Cre-mediated recombination. A key limitation was strong recombination bias favoring the proximal guides. Here, we effectively mitigated this bias by inactivating a recombination hotspot, yielding guide representation nearly as uniform as traditional lentiviral libraries. Applying this optimized platform, we systematically profiled 70 (52%) RNA modification factors across 46 mouse tissues, uncovering pervasive tissue-specific essentiality. Notably, iMAP displayed much higher essential gene recovery than prior lentiviral CRISPR screens, attributable to its stronger guide depletion and lower technical noise. Finally, in a tumor model, iMAP identified Thg1l as a repressor of NK cell TNF production; its ortholog knockout enhanced human NK cell-mediated tumor killing, underscoring therapeutic potential. All data are available in an interactive iMAP database. This work advances the Perturbation Atlas, a foundational resource for functional genomics. TeaserA unique CRISPR perturbation tool has been upgraded and deployed to reveal functions of epigenetic regulators in mice.

genomics↗

bioRxiv2025

Selective interaction of the protein SMCHD1 with specific chromatin regions is governed by the loading factor LRIF1 and SMCHD1 ATPase activity

The chromosomal protein SMCHD1 is a GHKL ATPase that plays important roles in epigenetic silencing, including on the inactive X chromosome (Xi) and at the D4Z4 macrosatellite linked to regulation of DUX4 expression in the disorders facioscapulohumeral muscular dystrophy (FSHD2) and Bosma arrhinia micropthalmia syndrome (BAMS). In this study we use live-cell and single-molecule imaging approaches to investigate SMCHD1 interactions with chromatin and its function in epigenetic silencing. We show that chromatin binding of SMCHD1 genome-wide, including on the Xi, is critically dependent on the protein LRIF1 that mediates interaction with H3K9me2/3 modified nucleosomes. Using engineered mutations in the GHKL ATPase domain we show that ATP hydrolysis is required for selective enrichment of SMCHD1 at specific chromatin regions, which is critical for gene silencing on the Xi. A gain-of-function mutation, G137E, that occurs in BAMS patients, results in accelerated Xi recruitment and greater Xi chromosome compaction. Together, our findings advance mechanistic understanding of SMCHD1 function on the Xi and at other target sites in the genome.

molecular biology↗

bioRxiv2025

Inhibition of DHODH Activates Pyroptosis and cGAS-STING Pathways to Enhance NK cell Infiltration Mediated Anti-tumor Immunity in Melanoma

Cancer cells are heavily reliant on de novo pyrimidine synthesis. Suppression of pyrimidine metabolism directly inhibits tumor growth and fosters immune activation within the tumor microenvironment. Dihydroorotate dehydrogenase (DHODH), a crucial enzyme governing de novo pyrimidine synthesis, is a critical player in this context. Inhibition of DHODH not only reverses immunosuppression but also instigates a mild innate immune response. However, the impact of DHODH inhibition on natural killer (NK) cells remains unexplored. In this study, we found that inhibition of DHODH efficiently promotes NK cells infiltration in tumors. Suppression of DHODH led to increased oxidative stress in mitochondria, the release of mtDNA, and activation of caspase 3, which in turn activated the cGAS-STING pathway and pyroptosis in cancer cells, respectively, contributing to NK cells induced antitumor immune responses in melanoma. Additionally, we developed EA6, a novel DHODH inhibitor with higher efficacy in promoting NK cells infiltration. In summary, this study underscores that modulation of pyrimidine metabolism can effectively trigger antitumor immune responses, with a specific emphasis on NK cells. This finding opens new avenues for enhancing the efficacy of targeted nucleotide metabolism in cancer therapy. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/644471v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@88d4fcorg.highwire.dtl.DTLVardef@156fe1aorg.highwire.dtl.DTLVardef@448086org.highwire.dtl.DTLVardef@152079c_HPS_FORMAT_FIGEXP M_FIG C_FIG The anti-tumor mechanisms of DHODH inhibition. Inhibition of DHODH activates cGAS-STING pathways to enhance NK cell infiltration. And the tumor-infiltrating NK cells facilitate melanoma cells pyroptosis which providing a positive feedback mechanism for DHODH-mediated anti-tumor immunity.

cancer biology↗

bioRxiv2025

N6-methyladenosine and the NEXT complex direct Xist RNA turnover and X inactivation dynamics

X chromosome inactivation (XCI) in mammals is orchestrated by the non-coding RNA Xist which together with specific interacting proteins, functions in cis to silence an entire X chromosome. Defined sites on Xist RNA carry the N6-methyladenosine (m6A) modification, and perturbation of the m6A writer complex has been found to abrogate Xist-mediated gene-silencing. However, the relative contribution of m6A and its mechanism of action remain unclear. Here we investigate the role of m6A in XCI by applying rapid degron-mediated depletion of METTL3, the catalytic subunit of the m6A writer complex, an approach that minimises indirect effects due to transcriptome-wide depletion of m6A. We find that acute loss of METTL3/m6A accelerates Xist-mediated gene silencing, and that this correlates with increased levels and stability of Xist transcripts. We show that Xist RNA turnover is mediated by the nuclear exosome targeting (NEXT) complex but is independent of the principal nuclear m6A reader protein YTHDC1. Our findings demonstrate that the primary function of m6A on Xist RNA is to promote Xist RNA turnover which in turn regulates XCI dynamics.

biochemistry↗