Biology subjects

Meierhofer, D.

Publications and source records attributed to Meierhofer, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Recording proteome dynamics in the late-stage embryo at hour-timescale, spatial, and single-cell resolution with MEMBRYO

Cell fate during development is directed by new gene expression states that replace prior ones. When and where a protein is first translated, and how long it will remain in the cell, dictate the timing and extent of a gene's phenotypic effect. Accessing protein synthesis and turnover information in the rapidly developing embryo remains a major challenge. Here we present MEMBRYO: a method for continuous stable isotope labeling (SILAC) of newly synthesized proteins throughout the live embryo at the hour-timescales of developmental phenotypes. We extend embryo culture into the late stages of organogenesis, thereby accessing the proteome of neurogenesis in the forebrain ex utero. Variations in protein synthesis and turnover activity lead to expression patterns that diverge from the corresponding transcripts, impacting molecular pathways and key milestones of cortical neuron differentiation. The high labeling depth enabled both spatial and single-cell SILAC proteomics analysis of cortical cells, revealing distinct layers of post-transcriptional gene expression regulation in progenitors and neurons. By continuous metabolic labeling in the live embryo, MEMBRYO tracks the past, present, and future of the developmental proteome.

developmental biology↗

bioRxiv2026

Evolution and mechanism of MEIS2-mediated forelimb specialization in bats

The genomic basis of limb adaptations in tetrapods is thought to be largely driven by changes in gene regulation. However, the mechanisms by which regulatory programs evolve are not well understood. In bats, wing membrane development has been shown to be associated with expression of the transcription factor MEIS2 in the interdigital tissue of the forelimb. However, MEIS2 alone is insufficient to recapitulate wing morphology, suggesting that its regulatory context has also undergone divergence. Here, we integrate functional genomics with sequence-to-function deep learning to dissect both the mechanistic and evolutionary roles of MEIS2 in bat forelimb development. Using models trained on embryonic limb data from bat and mouse, we identify a strong association between MEIS2 binding and the transcription factor TWIST1, a finding which is supported by single-cell transcriptomic analyses. To investigate the evolutionary dimension, we applied these models across more than 100 genomes, including extant bats, closely related species, and reconstructed ancestors. This analysis identified divergences in regulatory regions, which likely contribute to bat-specific forelimb expression of genes that lead to wing morphogenesis. Notably, these changes are prominent in the regulatory domains of the MEIS dimerization partner PBX1, indicating coordinated regulatory evolution. Together, our results demonstrate that the evolution of a complex morphological trait involves coordinated changes in both trans-regulatory environments and cis-regulatory landscapes. More broadly, this study provides a framework for integrating deep learning with comparative and functional genomics to investigate regulatory evolution.

evolutionary biology↗

bioRxiv2025

Microbial Priming Enhances TLR7-Driven Myddosome Assembly Dynamics

Cells can modify their future behavior based on prior exposures, a phenomenon known as cellular adaptation. In innate immunity, such adaptive responses are critical for fine-tuning host defense, enabling trained immunity or tolerance. These states have been largely attributed to long-lasting epigenetic or metabolic reprogramming. Whether prior microbial encounters can rapidly lower receptor signaling thresholds to selectively enhance responsiveness of individual innate immune receptors remains unknown. Here, we identify a previously unrecognized, non-genetic form of cellular adaptation. We show that TLR4 activation by LPS, while inducing classical endotoxin tolerance, simultaneously primes macrophages for enhanced responses to subsequent activation of the RNA sensor TLR7. Because TLR4 and TLR7 use the same signaling machinery, this indicates that they are selectively reprogrammed in this process. TLR7 training requires type I interferons and is marked by a strong increase in Myddosome assemblies at endosomal membranes, without changes in TLR7 abundance or ligand uptake. These findings reveal that innate immune training can be rapidly encoded at the level of receptor-proximal signaling, linking microbial priming to enhanced nucleic acid immunity and potentially to TLR7-driven autoimmunity in genetically predisposed individuals. Short summaryLPS priming drives receptor-proximal immune adaptation in macrophages, inducing classical TLR4 endotoxin tolerance while simultaneously sensitizing the RNA sensor TLR7 by enhancing Myddosome nucleation at endosomal membranes. This compartment- and receptor specific reprogramming may link prior infection history to elevated risk of TLR7-driven autoimmunity.

cell biology↗

bioRxiv2025

ATXN2 polyglutamine expansion impairs QKI-dependent alternative splicing and oligodendrocyte maintenance

BackgroundPolyglutamine (polyQ) tract expansion mutations in Ataxin-2 gene (ATXN2) are associated with neurodegenerative diseases spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS), while the therapeutic reduction of ATXN2 confers strong health-/lifespan extension in models of both disorders. Although the involvement of ATXN2 in peripheral lipid metabolism has been elaborated in Atxn2 knock-out mice, its impact on nervous system lipid maintenance and a potential influence on oligodendrocytes remains unexplored. MethodsWe examine the nervous tissue of an authentic ATXN2 polyQ expansion mouse model in terms of (i) gross morphology of the brain and differential glial affection via immunohistochemical analyses, (ii) spinocerebellar proteome profile via label-free mass spectroscopy and (iii) alternative splicing patterns of oligodendroglial transcripts via quantitative RT-PCR. Finally, electrophysiological recording of sensory response in cerebellar Purkinje cells was performed as a phenotypic measure of demyelination. ResultsWe demonstrate a massive impairment in myelin maintenance due to ATXN2 polyQ expansion, affecting key oligodendroglial proteins accompanied by their splicing anomalies much earlier than disease manifestation. Oligodendroglial ATXN2 aggregates were documented for the first time in cerebellum, which sequestrated the RNA splicing factor Quaking (QKI). As an outcome of demyelination, our SCA2 model showed a significant delay in response to sensory stimuli. ConclusionsOverall, we provide pioneer evidence of oligodendroglial proteotoxicity leading to myelin maintenance defects in an authentic mouse model of SCA2. Our findings suggest that not only neuronal metabolism, but also that of oligodendroglia depends on ATXN2 and is affected during the disease course. This novel aspect of ATXN2 pathomechanism sheds light on potential outcomes of its therapeutic manipulation, and makes it relevant also for demyelination syndromes next to SCA2 and other polyQ disorders.

neuroscience↗

bioRxiv2025

Multiomics approach identifies SERPINB1 as candidate progression biomarker for Spinocerebellar Ataxia type 2

BackgroundSpinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder, and variants in its disease protein Ataxin-2 act as modifiers in the progression of Amyotrophic Lateral Sclerosis. There are no reliable molecular progression biomarkers for SCA2. ObjectivesThe aim of this study was to define novel molecular progression biomarker candidates for SCA2. MethodsUsing cerebellar and cervicothoracic spinal cord RNA from Atxn2-CAG100-KnockIn and wildtype mice, a multi-omics study was conducted, followed by validation in mice and humans. Global transcriptome studies were conducted using the Clariom D microarray. Extracted proteins were analyzed by LC-MS/MS for global proteomics, and Immobilized Metal Affinity Chromatography for phosphoproteomics. Validation assessed expression by RT-qPCR, and protein abundance by quantitative immunoblots and ELISA. Patients with SCA2 were diagnosed following standard procedures, and the age at onset, SARA score, INAS count, and disease duration were used as clinical severity markers. ResultsVenn diagram comparisons across all OMICS datasets indicated that only Serpinb1a-transcript, SERPINB1A-protein and -phosphopeptides were consistently downregulated at terminal stage in 14-month-old KnockIn mice. Expression studies in cerebellum and spinal cord from 10 weeks (pre-manifest), 6-month-old (early ataxic), and 14-month-old (late ataxic stage) mice confirmed this progressive decrease at mRNA and protein level. SERPINB1 plasma levels were significantly lower in SCA2 patients, and displayed a significant association with the CAG repeat length at expanded ATXN2 alleles and the age at onset, also showing a trend towards significance with the SARA score. ConclusionsSERPINB1 was identified as novel promising biomarker with specificity for SCA2 pathomechanisms.

molecular biology↗

bioRxiv2025

ATXN2L primarily interacts with NUFIP2, the absence of ATXN2L results in NUFIP2 depletion, and the ATXN2-polyQ expansion triggers NUFIP2 accumulation

The cytoplasmic Ataxin-2 (ATXN2) protein associates with TDP-43 in stress granules (SG) where RNA quality control occurs. Mutations in this pathway underlie Spinocerebellar Ataxia type 2 (SCA2) and Amyotrophic Lateral Sclerosis. In contrast, Ataxin-2-like (ATXN2L) is predominantly nuclear, more abundant, and essential for embryonic life. Its sequestration into ATXN2 aggregates may contribute to disease. In this study, we utilized two approaches to clarify the roles of ATXN2L. First, we identified interactors through co-immunoprecipitation in both wild-type and ATXN2L-null murine embryonic fibroblasts. Second, we assessed the proteome profile effects using mass spectrometry in these cells. Additionally, we examined the accumulation of ATXN2L interactors in the SCA2 mouse model, Atxn2-CAG100-KnockIn (KIN). We observed that RNA-binding proteins, including PABPN1, NUFIP2, MCRIP2, RBMS1, LARP1, PTBP1, FMR1, RPS20, FUBP3, MBNL2, ZMAT3, SFPQ, CSDE1, HNRNPK, and HNRNPDL, exhibit a stronger association with ATXN2L compared to established interactors like ATXN2, PABPC1, LSM12, and G3BP2. Additionally, ATXN2L interacted with components of the actin complex, such as SYNE2, LMOD1, ACTA2, FYB, and GOLGA3. We noted that oxidative stress increased HNRNPK but decreased SYNE2 association, which likely reflects the relocalization of SG. Proteome profiling revealed that NUFIP2 and SYNE2 are depleted in ATXN2L-null fibroblasts. Furthermore, NUFIP2 homodimers and SYNE1 accumulate during the ATXN2 aggregation process in KIN 14-month-old spinal cord tissues. The functions of ATXN2L and its interactors are therefore critical in RNA granule trafficking and surveillance, particularly for the maintenance of differentiated neurons.

molecular biology↗

bioRxiv2023

Mutant Huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure

Expansion of the glutamine tract (poly-Q) in the protein Huntingtin (HTT) causes the neurodegenerative disorder Huntingtons disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. 70Q introduction caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics and elevated resting energy expenditure. Elimination of the poly-Q tract of HTT normalized CHCHD2 expression and mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early intervention target for HD.

neuroscience↗

bioRxiv2023

N4-acetylcytidine (ac4C) promotes mRNA localization to stress granules

Stress granules are an integral part of the stress response that are formed from non-translating mRNAs aggregated with proteins. While much is known about stress granules, the factors that drive their mRNA localization are incompletely described. Modification of mRNA can alter the properties of the nucleobases and affect processes as translation, splicing and localization of individual transcript. Here, we show that the RNA modification N4-acetylcytidine (ac4C) on mRNA associates with transcripts enriched in stress granules and that stress granule localized transcripts with ac4C are particularly translationally regulated. In addition, we show that ac4C on mRNA can mediate co-localization of the protein NOP58 to stress granules. Our results show that acetylation of mRNA regulates localization of both stress-sensitive transcripts and RNA-binding proteins to stress granules and adds to our understanding of the molecular mechanisms responsible for stress granule formation.

molecular biology↗

bioRxiv2023

Endosome dysfunction leads to gain-of-function TLR7 and human lupus

Hyperactive Toll-like receptor (TLR) 7 signaling has long been appreciated as a driver of autoimmune disease by breaking tolerance to self-nucleic acids in mouse models1-5. Recently, mutations in TLR7 or its associated regulator UNC93B16, 7, were identified as monogenic causes of human lupus; the unifying feature of these mutations being TLR7 gain-of-function. TLR7 is an intracellular transmembrane receptor, sensing RNA breakdown products within late endosomes8, 9. Hence, its function depends on intricate transport mechanisms and membrane interactions within the endomembrane network. Whether perturbations of any of these endosome-related processes can give rise to TLR7 gain-of-function and facilitate self-reactivity has not been investigated. Here, we show that a dysregulated endosomal compartment leads to unrestricted TLR7 signaling and human lupus. The late endosomal BLOC-1-related protein complex (BORC) together with the small Arf1-like GTPase Arl8b controls TLR7 protein levels, and a direct interaction between Arl8b and Unc93b1 is required to regulate TLR7 turnover. We identified an amino acid insertion in UNC93B1 in a patient with childhood-onset lupus, which reduces the interaction with the BORC-Arl8b complex and leads to endosomal TLR7 accumulation. Therefore, a failure to control the proper progression of TLR7 through its endocytic life cycle is sufficient to break immunological tolerance to nucleic acids in humans. Our results highlight the importance of an intact endomembrane system to prevent autoimmune disease. As the cellular mechanisms restricting TLR7 signaling can be manifold, identifying and stratifying lupus patients based on a TLR7-driven pathogenesis could be a viable strategy towards a targeted therapy.

immunology↗

bioRxiv2022

Discovery and characterization of LNCSOX17 as an essential regulator in human endoderm formation

Long non-coding RNAs (lncRNAs) have emerged as fundamental regulators in various biological processes, including embryonic development and cellular differentiation. Despite much progress over the past decade, the genome-wide annotation of lncRNAs remains incomplete and many known non-coding loci are still poorly characterized. Here, we report the discovery of a previously not annotated lncRNA that is transcribed upstream of the SOX17 gene and located within the same topologically associating domain. We termed it LNCSOX17 and show that it is induced following SOX17 activation but its expression is more tightly restricted to early definitive endoderm. Loss of LNCSOX17 affects crucial functions independent of SOX17 and leads to an aberrant endodermal transcriptome, signaling pathway deregulation and epithelial to mesenchymal transition defects. Consequently, cells lacking the lncRNA cannot further differentiate into more mature endodermal cell types. We identified and characterized LNCSOX17 as an essential new actor in early human endoderm, thereby further expanding the list of functionally important non-coding regulators.

genomics↗

bioRxiv2022

Metabolic enhancement of mammalian developmental pausing

The quest to model and modulate embryonic development became a recent cornerstone of stem cell and developmental biology. Mammalian developmental timing is adjustable in vivo by preserving preimplantation embryos in a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development in vitro, yet constraints to pause duration are unrecognized. By comparing the response of embryonic and extraembryonic stem cells to mTORi-induced pausing, we identified lipid usage as a bottleneck to developmental pausing. Enhancing fatty acid oxidation (FAO) boosts embryo longevity, while blocking it reduces the pausing capacity. Genomic and metabolic analyses of single embryos point toward a deeper dormant state in FAO-enhanced pausing and reveal a link between lipid metabolism and embryo morphology. Our results lift a constraint on in vitro embryo survival and suggest that lipid metabolism may be a critical metabolic transition relevant for longevity and stem cell function across tissues. One-Sentence SummaryFacilitating fatty acid oxidation by carnitine supplementation enhances mTOR inhibition-mediated developmental pausing.

developmental biology↗

bioRxiv2022

Androgen receptor condensates as drug targets

Transcription factors are among the most attractive therapeutic targets but are considered largely undruggable due to the intrinsically disordered nature of their activation domains. Here we show that the aromatic character of the activation domain of the androgen receptor, a therapeutic target for castration resistant prostate cancer, is key for its activity as a transcription factor by allowing it to partition into transcriptional condensates. Based on this knowledge we optimized the structure of a small molecule inhibitor, previously identified by phenotypic screening, that targets a specific transactivation unit within the domain that is partially folded and rich in aromatic residues. The optimized compounds had more affinity for their target, inhibited androgen receptor-dependent transcriptional programs, and had antitumorigenic effect in models of castration-resistant prostate cancer in cells and in vivo. These results establish a generalizable framework to target small molecules to the activation domains of oncogenic transcription factors and other disease-associated proteins with therapeutic intent.

biochemistry↗

bioRxiv2021

Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids

The cellular microenvironment together with intrinsic regulators shapes stem cell identity and differentiation capacity. Mammalian early embryos are exposed to hypoxia in vivo and appear to benefit from hypoxic culture in vitro. Yet, components of the hypoxia response and how their interplay impacts stem cell transcriptional networks and lineage choices remain poorly understood. Here we investigated the molecular effects of acute and prolonged hypoxia on distinct embryonic and extraembryonic stem cell types as well as the functional impact on differentiation potential. We find a temporal and cell type-specific transcriptional response including an early primitive streak signature in hypoxic embryonic stem (ES) cells. Using a 3D gastruloid differentiation model, we show that hypoxia-induced T expression enables symmetry breaking and axial elongation in the absence of exogenous WNT activation. Importantly, hypoxia also modulates T levels in conventional gastruloids and enhances representation of endodermal and neural markers. Mechanistically, we identify Hif1 as a central factor that mediates the transcriptional response to hypoxia in balance with epigenetic and metabolic rewiring. Our findings directly link the microenvironment to stem cell function and provide a rationale supportive of applying physiological conditions in models of embryo development

developmental biology↗

bioRxiv2021

Nuclear RNA-acetylation can be erased by the deacetylase SIRT7

A large number of RNA modifications are known to affect processing and function of rRNA, tRNA and mRNA 1. The N4-acetylcytidine (ac4C) is the only known RNA acetylation event and is known to occur on rRNA, tRNA and mRNA 2,3. RNA modification by acetylation affects a number of biological processes, including translation and RNA stability 2. For a few RNA methyl modifications, a reversible nature has been demonstrated where specific writer proteins deposit the modification and eraser proteins can remove them by oxidative demethylation 4-6. The functionality of RNA modifications is often mediated by interaction with reader proteins that bind dependent on the presence of specific modifications 1. The NAT10 acetyltransferase has been firmly identified as the main writer of acetylation of cytidine ribonucleotides, but so far neither readers nor erasers of ac4C have been identified 2,3. Here we show, that ac4C is bound by the nucleolar protein NOP58 and deacetylated by SIRT7, for the first time demonstrating reversal by another mechanism than oxidative demethylation. NOP58 and SIRT7 are involved in snoRNA function and pre-ribosomal RNA processing 7-10, and using a NAT10 deficient cell line we can show that the reduction in ac4C levels affects both snoRNA sub-nuclear localization and pre-rRNA processing. SIRT7 can deacetylate RNA in vitro and endogenous levels of ac4C on snoRNA increase in a SIRT7 deficient cell line, supporting its endogenous function as an RNA deacetylase. In summary, we identify the first eraser and reader proteins of the RNA modification ac4C, respectively, and suggest an involvement of RNA acetylation in snoRNA function and pre-rRNA processing.

molecular biology↗

bioRxiv2020

Enhanced inflammatory response mediated by parenchymal cells associates with resistance towards mTOR inhibition

Activation of the mTOR pathway is frequently found in cancer, but mTOR inhibitors have thus far failed to demonstrate significant antiproliferative efficacy in the majority of cancer types. Besides cancer cell-intrinsic resistance mechanisms, it is conceivable that mTOR inhibitors impact on non-malignant host cells in a manner that ultimately supports resistance of cancer cells. Against this background, we sought to analyze the functional consequences of mTOR inhibition in hepatocytes for the growth of metastatic colon cancer. To this end, we established a liver epithelial cell (LEC)-specific knock-out (KO) of mTOR (mTORLEC mice). We used these mice to characterize the growth of colorectal liver metastases with and without partial hepatectomy to model different clinical settings. While the LEC-specific loss of mTOR remained without effect on metastasis growth in intact liver, partial liver resection resulted in the formation of larger metastases in mTORLEC mice compared to wildtype controls. This was accompanied by significantly enhanced inflammatory activity in LEC-specific mTOR KO livers after partial liver resection. Analysis of NF-{kappa}B target gene expression and immunohistochemistry of p65 displayed a significant activation of NF-{kappa}B in mTORLEC mice, suggesting a functional importance of this pathway for the observed inflammatory phenotype. Taken together, we show an unexpected acceleration of liver metastases upon deletion of mTOR in liver epithelial cells. Our results support the notion that non-malignant host cells can contribute to resistance against mTOR inhibitors and encourage to test if anti-inflammatory drugs are able to improve the efficacy of mTOR inhibitor for cancer therapy.

cancer biology↗

bioRxiv2020

SON and SRRM2 form nuclear speckles in human cells

The nucleus of higher eukaryotes is a highly compartmentalized and dynamic organelle consisting of several biomolecular condensates that regulate gene expression at multiple levels (1, 2). First reported more than 100 years ago by Ramon y Cajal, nuclear speckles (NS) are among the most prominent of such condensates (3). Despite their prevalence, research on the function of NS is virtually restricted to colocalization analyses, since an organizing core, without which NS cannot form, remains unidentified (4, 5). The monoclonal antibody SC35, which was raised against a spliceosomal extract, is a frequently used reagent to mark NS since its debut in 1990 (6). Unexpectedly, we found that this antibody has been misidentified and the main target of SC35 mAb is SRRM2, a large ([~]300 kDa), spliceosomeassociated (7) protein with prominent intrinsically disordered regions (IDRs) that sharply localizes to NS (8). Here we show that, the elusive core of NS is formed by SON and SRRM2, since depletion of SON leads only to a partial disassembly of NS, while combined depletion of SON together with SRRM2, but not other NS associated factors, or depletion of SON in a cell line where IDRs of SRRM2 are genetically deleted, leads to a near-complete dissolution of NS. This work, therefore, paves the way to study the role of NS under diverse physiological and stress conditions.

molecular biology↗

bioRxiv2020

Cell autonomous requirement of Neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis

BackgroundNeurofibromatosis type 1 (NF1) is a multi-organ disease caused by mutations in Neurofibromin (NF1). Amongst other features, NF1 patients frequently show reduced muscle mass and strength, impairing patients mobility and increasing the risk of fall. The role of Nf1 in muscle and the cause for the NF1-associated myopathy is mostly unknown. MethodsTo dissect the function of Nf1 in muscle, we created muscle-specific knockout mouse models for Nf1, inactivating Nf1 in the prenatal myogenic lineage either under the Lbx1 promoter or under the Myf5 promoter. Mice were analyzed during pre-and postnatal myogenesis and muscle growth. ResultsNf1Lbx1 and Nf1Myf5 animals showed only mild defects in prenatal myogenesis. Nf1Lbx1 animals were perinatally lethal, while Nf1Myf5 animals survived only up to approx. 25 weeks. A comprehensive phenotypic characterization of Nf1Myf5 animals showed decreased postnatal growth, reduced muscle size, and fast fiber atrophy. Proteome and transcriptome analysis of muscle tissue indicated decreased protein synthesis and increased proteasomal degradation, and decreased glycolytic and increased oxidative activity in muscle tissue. High-resolution respirometry confirmed enhanced oxidative metabolism in Nf1Myf5 muscles, which was concomitant to a fiber type shift from type 2B to type 2A and type 1. Moreover, Nf1Myf5 muscles showed hallmarks of decreased activation of mTORC1 and increased expression of atrogenes. Remarkably, loss of Nf1 promoted a robust activation of AMPK with a gene expression profile indicative of increased fatty acid catabolism. Additionally, we observed a strong induction of genes encoding catabolic cytokines in muscle Nf1Myf5 animals, in line with a drastic reduction of white, but not brown adipose tissue. ConclusionsOur results demonstrate a cell-autonomous role for Nf1 in myogenic cells during postnatal muscle growth required for metabolic and proteostatic homeostasis. Furthermore, Nf1 deficiency in muscle drives cross-tissue communication and mobilization of lipid reserves.

developmental biology↗

bioRxiv2019

The effects of arbuscular mycorrhizal fungi (AMF) and Rhizophagus irregularis in soil microorganisms accessed by metatranscriptomics and metaproteomics

Arbuscular mycorrhizal fungi (AMF) form symbioses with approximately 80% of plant species and potentially benefit their hosts (e.g. nutrient acquisition) and the soil environment (e.g. soil aggregation). AMF also affect soil microbiota and soil multifunctionality. We manipulated AMF presence (via inoculation of non-sterile soil with Rhizophagus irregularis and using a hyphal compartment design) and used RNA-seq and metaproteomics to assess AMF roles in soil. The results indicated that AMF drove an active soil microbial community expressing transcripts and proteins related to nine metabolic functions, including the metabolism of C and N. We suggest two possible mechanisms: 1) the AMF hyphae produce exudates that select a beneficial community, or, 2) the hyphae compete with other soil microbes for available nutrients and consequently induce the community to mineralize nutrients from soil organic matter. We also identified candidate proteins that are potentially related to soil aggregation, such as Lpt and HSP60. Our results bridge microbial ecology and ecosystem functioning. We show that the AMF hyphosphere contains an active community related to soil respiration and nutrient cycling, thus potentially improving nutrient mineralization from soil organic matter and nutrient supply to the plants.

ecology↗