Biology subjects

Xu, W.

Publications and source records attributed to Xu, W..

At least 235 records · Page 13Linked to original sources

bioRxiv2021

Hippocampus-striatum wiring diagram revealed by directed stepwise polysynaptic tracing

The hippocampus and the striatum represent two major systems in the brain for learning, memory and navigation. Although they were traditionally considered as two parallel systems responsible for distinct types of learning or navigation, increasing evidence indicates a close synergetic or competitive interaction between them. Both the hippocampus and the striatum consist of multiple anatomical and functional domains. Besides the limited direct projection from the hippocampus to the ventral striatum, most of the functional interaction between them may be mediated by polysynaptic projections. Polysynaptic connectivity has been difficult to examine due to a lack of methods to continuously track the pathways in a controlled manner. Here we developed a novel approach for directed stepwise polysynaptic tracing by reconstituting a replication-deficient retrograde transneuronal virus - pseudorabies virus lacking gene IE180 (PRV{Delta}IE). We minimized PRV neurotoxicity by temporally restricting viral replication; and enabled both anatomical tracing and functional analysis of the circuits. With these tools, we delineated a hippocampus-striatum wiring diagram, which consists of pathways from specific functional domains in the hippocampus to corresponding domains in the striatum via distinct intermediate regions. This polysynaptic wring diagram provides a structural foundation for further elucidation of the interaction between the hippocampus and the stratum in multiple brain functions. Significance StatementWe created a new method for controlled stepwise tracing of polysynaptic neuronal circuits which also enables functional analysis of the circuits. With this method, we revealed the polysynaptic wiring diagram between the hippocampus and the striatum, two major brain structures centrally involved in learning, memory and spatial navigation. This wiring diagram demonstrates how specific anatomical domains in the hippocampus are connected to the specific domains in the striatum via distinct intermediate brain regions; thus it will help to elucidate the functional interaction between these two major memory and navigation systems. Our new method can be broadly applied to many other brain circuits for anatomical and functional analysis.

neuroscience↗

bioRxiv2021

Loss of Protein Kinase D2 Activity Protects Against Bleomycin-induced Dermal Fibrosis in Mice

BackgroundDermal fibrosis occurs in many human diseases, particularly systemic sclerosis (SSc) where persistent inflammation leads to collagen deposition and fiber formation in skin and multiple organs. The family of protein kinase D (PKD) has been linked to inflammatory responses in various pathological conditions, however, its role in inflammation-induced dermal fibrosis has not been well defined. Here, using a murine fibrosis model that gives rise to dermal lesions similar to those in SSc, we investigated the role of PKD in dermal fibrosis in mice lacking PKD2 activity. MethodsHomozygous kinase-dead PKD2 knock-in mice (PKD2SSAA/SSAA-KI) were obtained through intercrossing mice heterozygous for PKD2S707A/S711A (PKD2SSAA). The wild-type and KI mice were subjected to repeated subcutaneous injection of bleomycin (BLM) to induce dermal inflammation and fibrosis. As controls, mice were injected with PBS. At the end of the experiment, mouse skin at the injection site was dissected, stained, and analyzed for morphological changes and expression of inflammatory and fibrotic markers. PKD-regulated signaling pathways were examined by real-time RT-qPCR and Western blotting. In a separate experiment, BLM-treated mice were administered with or without a PKD inhibitor, CRT0066101 (CRT). The effects of CRT on dermal fibrosis were analyzed similarly. The identity of the PKD expressing cells were probed using myeloid lineage markers CD45, CD68 in BLM-treated mouse tissues. ResultsDermal thickness and collagen fibers of kinase-dead PKD2-KI mice were significantly reduced in response to BLM treatment as compared to the wild-type mice. These mice also exhibited reduced -smooth muscle actin (-SMA) and collagen expression. At molecular levels, both transforming growth factor {beta}1 (TGF-{beta}1) and interleukin-6 (IL-6) mRNAs were decreased in the KI mice treated with BLM as compared to those in the wild-type mice. Similarly, CRT significantly blocked BLM-induced dermal fibrosis and inhibited the expression of -SMA, collagen, and IL-6 expression. Further analysis indicated that PKD2 was mainly expressed in CD45+/CD68+ myeloid cells that could be recruited to the lesional sites to promote the fibrotic process of the skin in response to BLM. ConclusionsKnock-in of the kinase-dead PKD2 or inhibition of PKD activity in mice protected against BLM-induced dermal fibrosis by reducing dermis thickness and expression of fibrotic biomarkers including -SMA, collagen, and inflammatory/fibrotic mediators including TGF-{beta}1 and IL-6. PKD2 does this potentially through modulating the recruitment and function of myeloid cells in skin of BLM-treated mice. Overall, our study demonstrated a potential critical role of PKD catalytic activity in inflammation-induced dermal fibrosis.

genetics↗

bioRxiv2021

Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with ACE2 interface, which gives 2G1 ability to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar IC50 in vitro. In SARS-CoV-2 and Beta- and Delta-variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 could be potentially capable of dealing with emerging SARS-CoV-2 variants in future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

cell biology↗

bioRxiv2021

miR2105 regulates ABA biosynthesis via OsbZIP86-OsNCED3 module to contribute to drought tolerance in rice

Induced abscisic acid (ABA) biosynthesis plays an important role in plant tolerance to abiotic stresses, including drought, cold and salinity. However, regulation pathway of the ABA biosynthesis in response to stresses is unclear. Here, we identified a rice miRNA, osa-miR2105 (miR2105), which plays a crucial role in ABA biosynthesis under drought stress. Analysis of expression, transgenic rice and cleavage site showed that OsbZIP86 is a target gene of miR2105. Subcellular localization and luciferase activity assays showed that OsbZIP86 is a nuclear transcription factor. In vivo and in vitro analyses showed that OsbZIP86 directly binds to the promoter of OsNCED3, and interacts with OsSAPK10, resulting in enhanced-expression of OsNCED3. Transgenic rice plants with knock-down of miR2105 or overexpression of OsbZIP86 showed higher ABA content, more tolerance to drought, a lower rate of water loss, more stomatal closure than wild type rice ZH11 under drought stress. These rice plants showed no penalty with respect to agronomic traits under normal conditions. By contrast, transgenic rice plants with miR2105 overexpression, OsbZIP86 downregulation, or OsbZIP86 knockout displayed less tolerance to drought stress and other phenotypes. Collectively, our results show that a regulatory network of miR2105-OsSAPK10/OsbZIP86-OsNCED3 control ABA biosynthesis in response to drought stress. One-sentence summary miR2105-OsbZIP86-OsNCED3 module plays crucial role in mediating ABA biosynthesis to contribute to drought tolerance with no penalty with respect to agronomic traits under normal conditions.

molecular biology↗

bioRxiv2021

Inhibitory hippocampo-septal projection controls locomotion and exploratory behavior

Although the hippocampus is generally considered a cognitive center for spatial representation, learning and memory, increasing evidence supports its roles in regulation of locomotion. However, the neuronal mechanisms of hippocampal regulation of locomotion and exploratory behavior remain unclear. Here we found that the inhibitory hippocampo-septal projection bi-directionally controls locomotion speed of mice. Pharmacogenetic activation of these septum-projecting interneurons decreased locomotion and exploratory behavior. Similarly, activation of the hippocampus-originated inhibitory terminal in the medial septum reduced locomotion. On the other hand, inhibition of the hippocampus-originated inhibitory terminal increased locomotion. The locomotion-regulative roles were specific to the septal projecting interneurons as activation of hippocampal interneurons projecting to the retrosplenial cortex did not change animal locomotion. Therefore, this study reveals a specific long-range inhibitory output from the hippocampus in the regulation of animal locomotion.

neuroscience↗

bioRxiv2021

Copper(II) Gluconate Boosts the Anti-SARS-CoV-2 Effect of Disulfiram in Vitro

Disulfiram is a 70-year-old anti-alcoholism drug, while copper(II) gluconate (Cu(Glu)2) is a commonly used food additive or copper supplement. Here we disclose that the combination of disulfiram and copper(II) gluconate drastically enhances the anti-SARS-CoV-2 activity at the cellular level as compared to disulfiram or copper(II) gluconate alone. A 1:1 mixture of disulfiram and copper(II) gluconate shows an EC50 value of 154 nM against SARS-CoV-2 at the cellular level, much lower than the 17.45 M reported for disulfiram alone. Notably, previous clinical trials have shown that a combination of 250 mg disulfiram (0.843 mmol) and 8 mg copper(II) gluconate (0.0176 mmol) oral capsules per day is well tolerated (NCT03034135, NCT00742911). A preliminary mechanism is proposed to rationalize the observed promotional effect.

biochemistry↗

bioRxiv2021

A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx

The roles of bactericidal cathelicidins against bacterial infection have been extensively studied. However, the anti-bacterial property and mechanism of action of non-bactericidal cathelicidins are rarely known. Herein, a novel naturally occurring cathelicidin (PopuCATH) from tree frog (Polypedates puerensis) didnt show any direct anti-bacterial activity in vitro. Intriguingly, intraperitoneal injection of PopuCATH before bacterial inoculation significantly reduced the bacterial load in tree frogs and mice, and reduced the inflammatory response induced by bacterial inoculation in mice. PopuCATH pretreatment also increased the survival rates of septic mice induced by a lethal dose of bacterial inoculation or cecal ligation and puncture (CLP). Intraperitoneal injection of PopuCATH significantly drove the leukocyte influx in both frogs and mice. In mice, PopuCATH rapidly drove neutrophil, monocyte/macrophage influx in mouse abdominal cavity and peripheral blood with a negligible impact on T and B lymphocytes, and neutrophils, monocytes/macrophages, but not T and B lymphocytes, were required for the preventive efficacy of PopuCATH. PopuCATH did not directly act as chemoattractant for phagocytes, but PopuCATH obviously drove phagocyte migration when it was cultured with macrophages. PopuCATH significantly elicited chemokine/cytokine production in macrophages through activating p38/ERK mitogen-activated protein kinases (MAPKs) and NF-{kappa}B p65. PopuCATH markedly enhanced neutrophil phagocytosis via promoting the release of neutrophil extracellular traps (NETs). Additionally, PopuCATH showed low side effects both in vitro and in vivo. Collectively, PopuCATH acts as a host-based immune defense regulator that provides prophylactic efficacy against bacterial infection without direct antimicrobial effects. Our findings reveal a non-bactericidal cathelicidin which possesses unique anti-bacterial action, and highlight the potential of PopuCATH to prevent bacterial infection.

immunology↗

bioRxiv2021

Spatial and Texture Analysis of Root System Architecture with Earth Mover's Distance

PurposeRoot system architectures are complex and challenging to characterize effectively for agronomic and ecological discovery. MethodsWe propose a new method, Spatial and Texture Analysis of Root SystEm distribution with Earth movers Distance (STARSEED), for comparing root system distributions that incorporates spatial information through a novel application of the Earth Movers Distance (EMD). ResultsWe illustrate that the approach captures the response of sesame root systems for different genotypes and soil moisture levels. STARSEED provides quantitative and visual insights into changes that occur in root architectures across experimental treatments. ConclusionSTARSEED can be generalized to other plants and provides insight into root system architecture development and response to varying growth conditions not captured by existing root architecture metrics and models. The code and data for our experiments are publicly available: https://github.com/GatorSense/STARSEED.

plant biology↗

bioRxiv2021

Assembly status transition offers an avenue for activity modulation of a supramolecular enzyme

Nature has evolved many supramolecular proteins assembled in certain, sometimes even seemingly oversophisticated, morphological manners. The rationale behind such evolutionary efforts is often poorly understood. Here we provide atomic-resolution insights into how the dynamic building of a structurally complex enzyme with higher-order symmetry offers amenability to intricate allosteric regulation. We have established the functional coupling between enzymatic activity and protein morphological states of glutamine synthetase (GS), an old multi-subunit enzyme essential for cellular nitrogen metabolism. Cryo-EM structure determination of GS in both the catalytically active and inactive assembly states allows us to reveal an unanticipated self-assembly-induced dynamics-driven allosteric paradigm, in which the remote interactions between two subcomplex entities significantly rigidify the otherwise structurally fluctuating active sites, thereby regulating activity. We further show in vivo evidences that how the enzyme morphology transitions could be modulated by cellular factors on demand. Collectively, our data present an example of how assembly status transition offers an avenue for allosteric modulation, and sharpens our mechanistic understanding of allostery, dynamics, cooperativity, and other complex functional and regulatory properties of supramolecular enzymes.

biochemistry↗

bioRxiv2021

Characterisation of the Ubiquitin-ESCRT pathway in Asgard archaea sheds new light on origins of membrane trafficking in eukaryotes

The ESCRT machinery performs a critical role in membrane remodelling events in all eukaryotic cells, including in membrane trafficking, membrane repair, cytokinetic abscission, in viral egress, and in the generation of extracellular vesicles. While the machinery is complex in modern day eukaryotes, where it comprises dozens of proteins, the system has simpler and more ancient origins. Indeed, homologues of ESCRT-III and the Vps4 ATPase, the proteins that execute the final membrane scission reaction, play analogous roles in cytokinesis and potentially in extracellular vesicle formation in TACK archaea where ESCRT-I and II homologues seem to be absent. Here, we explore the phylogeny, structure, and biochemistry of homologues of the ESCRT machinery and the associated ubiquitylation system found in genome assemblies of the recently discovered Asgard archaea. In these closest living prokaryotic relatives of eukaryotes, we provide evidence for the ESCRT-I and II sub-complexes being involved in the ubiquitin-directed recruitment of ESCRT-III,_as it is in eukaryotes. This analysis suggests a pre-eukaryotic origin for the Ub-coupled ESCRT system and a likely path of ESCRT evolution via a series of gene duplication and diversification events.

cell biology↗

bioRxiv2021

Repair of Noise-Induced Damage to Stereocilia F-actin Cores is Facilitated by XIRP2

Prolonged exposure to loud noise has been shown to affect inner ear sensory hair cells in a variety of deleterious manners, including damaging the stereocilia core. The damaged sites can be visualized as "gaps" in phalloidin staining of F-actin, and the enrichment of monomeric actin at these sites, along with an actin nucleator and crosslinker, suggests that localized remodeling occurs to repair the broken filaments. Herein we show that gaps in mouse auditory hair cells are largely repaired within one week of traumatic noise exposure through the incorporation of newly synthesized actin. Additionally, we report that XIRP2 is required for the repair process and facilitates the enrichment of monomeric{gamma} -actin at gaps through its LIM domain-containing C-terminus. Our study describes a novel process by which hair cells can recover from sub-lethal hair bundle damage and which may contribute to recovery from temporary hearing threshold shifts and the prevention of age-related hearing loss.

neuroscience↗

bioRxiv2021

E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis

Gasdermin D (GSDMD) participates in activation of inflammasomes and pyroptosis. Meanwhile, ubiquitination strictly regulates inflammatory responses. However, how ubiquitination regulates Gasdermin D activity is not well understood. In this study, we show that pyroptosis triggered by Gasdermin D is regulated through ubiquitination. Specifically, SYVN1, an E3 ubiquitin ligase of gasdermin D, promotes GSDMD-mediated pyroptosis. SYVN1 deficiency inhibits pyroptosis and subsequent LDH release and PI uptake. SYVN1 directly interacts with GSDMD, and mediates K27-linked polyubiquitination of GSDMD on K203 and K204 residues, promoting GSDMD-induced pyroptotic cell death. Thus, our findings revealed the essential role of SYVN1 in GSDMD-mediated pyroptosis. Overall, GSDMD ubiquitination is a potential therapeutic module for inflammatory diseases.

immunology↗

bioRxiv2021

Previously unrecognized non-reproducible antibody-antigen interactions and their implications for diagnosis of viral infections including COVID-19

Antibody-antigen (Ab-Ag) interactions are canonically described by a model which exclusively accommodates non-interaction (0) or reproducible-interaction (RI) states, yet this model is inadequate to explain often-encountered non-reproducible signals. Here, by monitoring diverse experimental systems and confirmed COVID-19 clinical sera using a peptide microarray, we observed that non-specific interactions (NSI) comprise a substantial proportion of non-reproducible antibody-based results. This enabled our discovery and capacity to reliably identify non-reproducible Ab-Ag interactions (NRI), as well as our development of a powerful explanatory model ("0-RI-NRI-Hook four-state model") that is [mAb]-dependent, regardless of specificity, which ultimately shows that both NSI and NRI are not predictable yet certain-to-happen. In experiments using seven FDA-approved mAb drugs, we demonstrated the use of NSI counts in predicting epitope type. Beyond challenging the centrality of Ab-Ag interaction specificity data in serology and immunology, our discoveries also facilitated the rapid development of a serological test with uniquely informative COVID-19 diagnosis performance.

immunology↗

bioRxiv2021

Structural model of PORCN illuminates disease-associated variants and drug binding sites

Wnt signaling is essential for normal development and is a therapeutic target in cancer. The enzyme PORCN, or porcupine, is a membrane-bound O-acyltransferase (MBOAT) that is required for the post-translational modification of all Wnts, adding an essential mono-unsaturated palmitoleic acid to a serine on the tip of Wnt hairpin 2. Inherited mutations in PORCN cause focal dermal hypoplasia, and therapeutic inhibition of PORCN slows the growth of Wnt-dependent cancers. Here, based on homology to mammalian MBOAT proteins we develop and validate a molecular structural model of PORCN. The model accommodates palmitoleoyl-CoA and Wnt hairpin 2 in two tunnels in the conserved catalytic core, shedding light on the catalytic mechanism. The model predicts how previously uncharacterized human variants of uncertain significance can alter PORCN function. Drugs including ETC-159, IWP-L6 and LGK-974 dock in the PORCN catalytic site, providing insights into PORCN pharmacologic inhibition. This structural model provides mechanistic insights into PORCN substrate recognition and catalysis as well as the inhibition of its enzymatic activity and can facilitate the development of improved inhibitors and the understanding of disease relevant PORCN mutants.

molecular biology↗

bioRxiv2021

Plakoglobin and HMGB1 mediate intestinal epithelial cell apoptosis induced by Clostridioides difficile TcdB

Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated intestinal disease, resulting in severe diarrhea and fatal pseudomembranous colitis. TcdB, one of the essential virulence factors secreted by this bacterium, induces host cell apoptosis through a poorly understood mechanism. Here, we performed an RNAi screen customized to Caco-2 cells, a cell line model of the intestinal epithelium, to discover host factors involved in TcdB-induced apoptosis. We identified plakoglobin, also known as junction plakoglobin (JUP) or {gamma}-catenin, a member of the catenin family, as a novel host factor, and a previously known cell death-related chromatin factor, high mobility group box 1 (HMGB1). Disruption of those host factors by RNAi and CRISPR resulted in resistance of cells to TcdB-mediated and mitochondria-dependent apoptosis. JUP was redistributed from adherens junctions to the mitochondria and colocalized with Bcl-XL after stimulation by TcdB, suggesting a role of JUP in cell death signaling through mitochondria. Treatment with glycyrrhizin, an HMGB1 inhibitor, resulted in significantly increased resistance to TcdB-induced epithelial damage in cultured cells and a mouse ligated colon loop model. These findings demonstrate the critical roles of JUP and HMGB1 in TcdB-induced epithelial cell apoptosis.

microbiology↗

bioRxiv2021

Distinct Hippocampal Neuronal Reactions Reveal Different Neuronal Codes for Memory Generalization

To survive in an ever-changing world we need to learn and memorize associations of environmental stimuli and generalize them to new situations. Both memory and generalization critically rely on the hippocampus, but it is unclear how hippocampal neuronal activities represent memory and generalization, and if a conserved hippocampal mechanism serves these functions. Here we compared neuronal activities in hippocampal CA1 region of two sub-strains of the widely used C57BL/6 mice, C57BL/6J (B6J) and C57BL/6NCrl (B6NCrl), in contextual fear conditioning. Both sub-strains learnt well but differed in freezing and generalization. They displayed distinct early-late bi-phasic reactions to the unconditioned stimulus. While in both sub-strains the neurons showing late-phase reactions were preferentially engaged in memory representation, the neuronal activity feature that correlated with generalization level differed in the two sub-strains: in B6NCrl, these neurons activity level during learning negatively correlated with the generalization level; in B6J, functional coupling of these late-phase neurons with other neurons positively correlated with the generalization level. We further found that the distinct neuronal reactions were accompanied by distinct GABAb receptor-mediated inhibition but not by differences in the major synaptic inputs or neuronal excitability of the CA1. Therefore, this comparative study reveals two signature neuronal activity features in learning that can predict generalization levels. The results also demonstrate that differences in hippocampal network properties lead to diverse hippocampal mechanisms in memory encoding and generalization.

neuroscience↗

bioRxiv2021

RiboTRIBE: Monitoring Translation with ADAR-meditated RNA Editing

RNA translation is tightly regulated to ensure proper protein expression in cells and tissues. Translation is often assayed with biochemical assays such as ribosome profiling and TRAP, which are effective in many contexts. These assays are however not ideal with limiting amounts of biological material when it can be difficult or even impossible to make an extract with sufficient signal or sufficient signal:noise. Because of our interest in translational regulation within the few Drosophila adult circadian neurons, we fused the ADAR catalytic domain (ADARcd) to several small subunit ribosomal proteins and assayed mRNA editing in Drosophila S2 cells. The strategy is named RiboTRIBE and is analogous to a recently published APOBEC-based method. The list of RiboTRIBE-edited transcripts overlaps well with ribosome profiling targets, especially with more highly ranked targets. There is also an enriched number of editing sites in ribosome-associated mRNA comparing to total mRNA, indicating that editing occurs preferentially on polyribosome-associated transcripts. The use of cycloheximide to freeze translating ribosomes causes a substantial increase in the number of RiboTRIBE targets, which is decreased by pretreating cells with the chain terminating drug puromycin. NOTE: Additional experiments performed after first submitting this manuscript to BioRxiv estimate that less than 5% of Rps28b-ADAR is ribosome-associated. This is because the vast majority of the fusion protein sediments at the top of a polyribosome gradient. We therefore suggest that most editing reported in the manuscript is not catalyzed by ribosome-associated ADAR (10/2/2021).

molecular biology↗

bioRxiv2021

Transcription factor-like 5 is a potential DNA/RNA-binding protein essential for maintaining male fertility in mice.Running title: Tcfl5 is haploinsufficient in vivo

Tissue-specific transcription factors often play key roles in the development of specific cell lineages. Transcription factor-like 5 (TCFL5) is a testis-specific protein that contains the basic helix-loop-helix domain, although the in vivo functions of TCFL5 remain unknown. Herein, we generated CRISPR/Cas9-mediated knockout mice to dissect the function of TCFL5 in mouse testes. Surprisingly, we found that it was difficult to generate homozygous mice with the Tcfl5 deletion since the heterozygous males (Tcfl5+/-) were infertile. We did, however, observe markedly abnormal phenotypes of spermatids and spermatozoa in the testes and epididymides of Tcfl5+/- mice. Mechanistically, we demonstrated that TCFL5 transcriptionally regulated a set of genes participating in male germ cell development, which we uncovered via RNA-sequencing and TCFL5 ChIP-sequencing. We also found that TCFL5 interacted with RNA-binding proteins (RBPs) that regulated RNA processing, and further identified the fragile X mental retardation gene 1, autosomal homolog (FXR1, a known RBP) as an interacting partner of TCFL5 that may coordinate the transition and localization of TCFL5 in the nucleus. Collectively, we herein report for the first time that Tcfl5 is haploinsufficient in vivo and hypothesize that TCFL5 may be a dual-function protein that mediates DNA and RNA to regulate spermatogenesis.

cell biology↗