Biology subjects

Ding, Y.

Publications and source records attributed to Ding, Y..

At least 127 records · Page 7Linked to original sources

bioRxiv2024

Conserved mycobacterial sRNA B11 regulates lipooligosaccharide synthesis at post-transcriptional level

Extractable glycolipids of mycobacteria, such as lipooligosaccharides (LOS), play key roles in responding to environmental stress and altering the host immune response. However, although the biosynthesis of LOS is likely controlled at multiple levels to ensure proper composition of the cell wall, the key regulators are currently unknown. Here, we studied B11, a conserved mycobacterial sRNA, and found that it post-transcriptionally regulates LOS synthesis in Mycobacteria marinum. Deletion of B11 alters the colony morphology and RNA sequencing combined with mass spectrometry identified several genes in the LOS synthesis locus that are regulated by B11. We found that B11 uses the cytosine-rich loops of its rho-independent transcriptional terminator to interact with guanine-tracks adjacent to the ribosome binding sites of its target genes, thereby impeding translation and promoting mRNA degradation by RNase E. These comprehensive functional studies of mycobacterial sRNA B11 demonstrate sRNA-based regulation of cell wall synthesis in mycobacteria. ImportanceDespite being identified for more than a decade, the functional characterization and regulatory mechanisms of mycobacterial sRNAs remain largely unexplored. We present here the most comprehensive functional study of mycobacterial sRNAs to date, employing convincible target screening using multifaceted experimental approaches and phenotype analysis. Our work reveals how synthesis of mycobacterial lipooligosaccharides (LOS), one of the crucial extractable glycolipids involved in environmental stress response and host immune modulation, is regulated at the post-transcriptional level by the conserved sRNA B11. Furthermore, our discovery of a highly conserved sRNA exhibiting distinct functions across mycobacterial species exemplifies divergent functional evolution among sRNAs.

microbiology↗

bioRxiv2024

Cell Maps for Artificial Intelligence: AI-Ready Maps of Human Cell Architecture from Disease-Relevant Cell Lines

This article describes the Cell Maps for Artificial Intelligence (CM4AI) project and its goals, methods, standards, current datasets, software tools, status, and future directions. CM4AI is the Functional Genomics Data Generation Project in the U.S. National Institute of Healths (NIH) Bridge2AI program. Its overarching mission is to produce ethical, AI-ready datasets of cell architecture, inferred from multimodal data collected for human cell lines, to enable transformative biomedical AI research.

systems biology↗

bioRxiv2024

Unbiased metastatic niche-labeling identifies estrogen receptor-positive macrophages as a barrier of T cell infiltration during bone colonization

Microenvironment niches determine cellular fates of metastatic cancer cells. However, robust and unbiased approaches to identify niche components and their molecular profiles are lacking. We established Sortase A-Based Microenvironment Niche Tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastatic colonization. SAMENT was applied to multiple cancer models colonizing the same organ and the same cancer to different organs. Common metastatic niche features include macrophage enrichment and T cell depletion. Macrophage niches are phenotypically diverse between different organs. In bone, macrophages express the estrogen receptor alpha (ER) and exhibit active ER signaling in male and female hosts. Conditional knockout of Esr1 in macrophages significantly retarded bone colonization by allowing T cell infiltration. ER expression was also discovered in human bone metastases of both genders. Collectively, we identified a unique population of ER+ macrophages in the metastatic niche and functionally tied ER signaling in macrophages to T cell exclusion during metastatic colonization. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/593016v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@1cd65b6org.highwire.dtl.DTLVardef@1d099e2org.highwire.dtl.DTLVardef@26cd91org.highwire.dtl.DTLVardef@181f5f3_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LISAMENT is a robust metastatic niche-labeling approach amenable to single-cell omics. C_LIO_LIMetastatic niches are typically enriched with macrophages and depleted of T cells. C_LIO_LIDirect interaction with cancer cells induces ER expression in niche macrophages. C_LIO_LIKnockout of Esr1 in macrophages allows T cell infiltration and retards bone colonization. C_LI

cancer biology↗

bioRxiv2024

Single cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization.

Bone represents congenial soil for metastatic seeds and is frequently affected by metastasis of multiple cancer types. The histological and molecular characteristics of bone metastases (BMs) are diverse but poorly understood. Herein, we performed single-cell RNA-seq on 34 BMs from 6 cancer types and identified 3 ecosystem archetypes characterized by enrichment of macrophages/osteoclasts (M{varphi}-OC), regulatory/exhausted T cells (Treg-Tex), and monocytes (Mono), respectively. Breast cancer BMs are mostly the M{varphi}-OC archetype driven by the osteolytic vicious cycle, whereas kidney cancers BMs mainly belong to the Treg-Tex archetype that lacks osteoclasts. Lung cancers BMs evenly distributed across all archetypes. Further analyses revealed parallel mechanisms of immunosuppression and bone remodeling. Elevated estrogen signaling distinguishes macrophages in the M{varphi}-OC subtype, which was investigated in a companion study. Together, we elucidated that divergent mechanisms toward bone colonization and that BMs of different origins can adopt the same mechanism through convergent evolution or adaptation. HIGHLIGHTSO_LIAnalyses of bone metastases from 6 cancer types revealed three immune archetypes. C_LIO_LIArchetypes diverge on immune trajectories, and features of tumor and stromal cells. C_LIO_LIDominant cell type in each archetype undergoes convergent evolution. C_LIO_LIRegulatory networks converge on osteoclasts and Tregs to drive archetype formation. C_LI Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/593027v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@82cef6org.highwire.dtl.DTLVardef@1e1b021org.highwire.dtl.DTLVardef@1f2881eorg.highwire.dtl.DTLVardef@1c6874a_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Neuromechanical Phase Lags and Gait Adaptation in the Nematode C. elegans

Undulation is a locomotor strategy in which waves of bending propagate along the body.This form of locomotion is observed in organisms that span orders of magnitude in size and represent diverse habitats and species. Despite this diversity, common neuromechanical phenomena have been observed across biologically disparate undulators, due to common mechanics. For example, Neuromechanical Phase Lags (NPL), a phenomenon where waves of muscle contraction travel at different speeds than body bends, have been observed in fish, lamprey and lizards. Existing theoretical descriptions of this phenomenon implicate the role of physical body-environment interactions. However, systematic experimental variation of body-environment interactions and measurement of the corresponding phase lags has not been performed. Using the nematode Caenorhabditis elegans we measured muscle and body curvature dynamics simultaneously, performing calcium imaging in the body wall muscles while systematically varying the environmental rheology. A mechanical model demonstrates that the measured phase lags are controlled by the relative strength of elastic torques within the body and resistive forces within the medium. We further show that the phase lags correspond with a difference in the wavenumber of the muscle activity and curvature patterns. Hence, the environmental forces that create NPL also act as a filter that shapes and modulates the gait commanded by the nervous system. Beyond nematodes, the simplicity of our model further suggests that tuning body elasticity may serve as a general means of modulating the degree of mechanical control in other undulators.

biophysics↗

bioRxiv2024

Development of the overlapping network modules in the human brain

Developmental connectomic studies have shown that the modular organization of functional networks in the human brain undergoes substantial reorganization with age to support cognitive growth. However, these studies implicitly assume that each brain region belongs to one and only one specific network module, ignoring the potential spatial overlap between functional modules. How the overlapping functional modular architecture develops and whether this development is related to structural signatures remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6-14 years), we investigated the development of the overlapping modular architecture of functional networks, and further explored their structural associations. Specifically, an edge-centric network model was used to identify the overlapping functional modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a remarkable regional inhomogeneity in module overlap in children, with higher entropy in the ventral attention, somatomotor, and subcortical networks and lower entropy in the visual and default-mode networks. Furthermore, the overlapping modules developed in a linear, spatially dissociable manner from childhood to adolescence, with significantly reduced entropy in the prefrontal cortex and putamen and increased entropy in the parietal lobules. Personalized overlapping modular patterns capture individual brain maturity as characterized by brain age. Finally, the overlapping functional modules can be significantly predicted by integrating gray matter morphology and white matter network properties. Our findings highlight the maturation of overlapping network modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.

neuroscience↗

bioRxiv2024

Super homotypic targeting by exosome surface engineering

Homotypic targeting is the inherent ability of cells for preferential interaction with cells of similar or identical types, a phenomenon commonly seen in cell adhesion, tissue formation, and immune responses. Unfortunately, its full potential remains largely untapped. Here we introduce an approach to drastically boost the homotypic targeting capabilities of cells via exosomes (nanoscale extracellular vesicles secreted by cells). By engineering exosome surfaces with lanthanides, we amplify specific cell-exosome interactions by more than 25-fold, significantly accelerating the selective capture of exosomes by cells of the same lineage. This substantial enhancement in cellular homophilicity opens up an entirely new class of applications, two of which we showcase here with unprecedented performance: using cells to detect specific exosomes and using exosomes to detect specific cells. The concept of "super homotypic targeting" offers enormous potential to transform cancer diagnostics, immunotherapy, targeted drug delivery, tissue engineering, and vaccine development.

cell biology↗

bioRxiv2024

The enhancement of electricity generation using cellulose based on ternary microbial consortium

Cooperation between microorganisms is crucial to design an efficient inoculum for enhancing the electricity-producing ability of carboxymethyl cellulose (CMC) fed bioreactors. In the present study, the influence of microbial mutualistic interactions and electricity generation capability were investigated by designing several co-culture and ternary culture systems. It was found that a ternary culture system of Cellulomonas Lsc-8, Bacillus subtilis C9 and Geobacter sulfurreducens PCA was used to efficiently convert cellulose into electricity. The maximum current density of 796 {+/-} 30 {micro}A{middle dot}cm-2 were achieved by the ternary culture, which were much higher than that Geobacter sulfurreducens PCA using acetate and co-culture systems to utilize CMC in bioreactors, respectively. In this consortium, Cellulomonas Lsc-8, and Bacillus subtilis C9 simultaneously digested CMC to produce acetate and secreted riboflavin as an electron shuttle; Geobacter sulfurreducens PCA utilized acetate to generate electricity. The introduction of Bacillus subtilis C9 further promoted the degradation of CMC and secreted more riboflavin to enhance electricity generation of the ternary culture. This work suggested that the synergistic interaction between interspecies in microbial consortia is emergent in designing specific community for achieving maximum power generation using CMC as substrate. This research shows new insight into the design of more efficient, stable, and robust microbial consortia applicable in waste treatment and power generation. IMPORTANCEMicrobial fuel cells (MFCs) may benefit from microbial consortia that efficiently convert carbon sources to electricity. A key challenge with this system is how to manage microbial community assembly to maximize electricity generation. Herein, we constructed and tested a three-species microbial consortium to enhance conversion of cellulose to electricity. Cellulomonas Lsc-8 and Bacillus subtilis C9 efficiently converted cellulose to acetate (electron donor) and riboflavin (electron shuttle), which enabled Geobacter sulfurreducens to generate electricity. This study laid the foundation for design of more efficient, stable, and robust microbial consortia for waste treatment and energy applications.

microbiology↗

bioRxiv2024

Circular DNA vcDNA-S7 derived from segmented-dsRNA virus BmCPV attenuated viral infection through RNase H1

Viral circDNA derived from insect positive-sense single-stranded RNA viruses plays a crucial role in regulating viral infections depending on the RNAi pathway. Our previous research has revealed that Bombyx mori cypovirus (BmCPV), a segmented-dsRNA virus, can generate viral circDNA vcDNA-S7, which can be transcribed to form RNA and further processed into small RNAs to defend against the virus through RNAi. However, whether vcDNA-S7 employs other mechanisms to resist the viruses. Presently, vcDNA-S7 has been found to resist BmCPV infection via a novel mechanism that depends on ribonuclease RNase H1 activity. It was found that the expression level of RNase H1 increased upon BmCPV infection (RNA virus) but not upon B. mori nucleopolyhedrovirus (BmNPV) (DNA virus) infection. RNase H1 has been shown to negatively regulate BmCPV infections. In addition, vcDNA-S7 was found to form a heteroduplex with the viral RNA and subsequently recruit RNase H1 to degrade the viral RNA within the heteroduplex, ultimately leading to the suppression of viral replication. Furthermore, the resistance of vcDNA-S7 to viruses was significantly reduced when cellular RNase H1 gene was silenced. These findings not only reveal a new antiviral mechanism involving circular DNA formed by reovirus but also offer intriguing insights into the antiviral function of RNase H1 in cells.

immunology↗

bioRxiv2024

Loss of Lkb1 cooperates with BrafV600E and UV radiation increasing melanoma multiplicity and neural-like dedifferentiation

The mechanisms cooperating with BRAFV600E oncogene in addition to ultraviolet (UV) radiation in melanoma development are of great interest. Analysis of human melanoma tumors (TCGA) indicates that 50% or more of the samples express no or low amounts of LKB1 protein. Here, we report that the concomitant neonatal BrafV600E activation and Lkb1 tumor suppressor ablation in melanocytes led to full melanoma development. A postnatal single-dose of UVB radiation had no effect on melanoma onset in Lkb1-depleted mice in respect to BrafV600E-irradiated mice, but increased tumor multiplicity. In agreement to this and previous reports, Lkb1 null irradiated mice showed a deficient DNA damage repair (DDR). Histologically, tumors lacking Lkb1 were enriched in neural-like tumor morphology. Genetic profiling and gene set enrichment analyses of tumor samples-mutated genes indicated that loss of Lkb1 promoted the selection of altered genes associated to neural differentiation processes. Thus, these results suggest that loss of Lkb1 cooperates with BrafV600E and UVR impairing DDR and increasing melanoma multiplicity and neural-like dedifferentiation.

cancer biology↗

bioRxiv2024

CPT1A Mediates Radiation Sensitivity in Colorectal Cancer

The prevalence and mortality rates of colorectal cancer (CRC) are increasing worldwide. Radiation resistance hinders radiotherapy, a standard treatment for advanced CRC, leading to local recurrence and metastasis. Elucidating the molecular mechanisms underlying radioresistance in CRC is critical to enhance therapeutic efficacy and patient outcomes. Bioinformatic analysis and tumour tissue examination were conducted to investigate the CPT1A mRNA and protein levels in CRC and their correlation with radiotherapy efficacy. Furthermore, lentiviral overexpression and CRISPR/Cas9 lentiviral vectors, along with in vitro and in vivo radiation experiments, were used to explore the effect of CPT1A on radiosensitivity. Additionally, transcriptomic sequencing, molecular biology experiments, and bioinformatic analyses were employed to elucidate the molecular mechanisms by which CPT1A regulates radiosensitivity. CPT1A was significantly downregulated in CRC and negatively correlated with responsiveness to neoadjuvant radiotherapy. Functional studies suggested that CPT1A mediates radiosensitivity, influencing reactive oxygen species (ROS) scavenging and DNA damage response. Transcriptomic and molecular analyses highlighted the involvement of the peroxisomal pathway. Mechanistic exploration revealed that CPT1A downregulates the FOXM1-SOD1/SOD2/CAT axis, moderating cellular ROS levels after irradiation and enhancing radiosensitivity. CPT1A downregulation contributes to radioresistance in CRC by augmenting the FOXM1-mediated antioxidant response. Thus, CPT1A is a potential biomarker of radiosensitivity and a novel target for overcoming radioresistance, offering a future direction to enhance CRC radiotherapy.

cancer biology↗

bioRxiv2024

Normative growth modeling of brain morphology reveals neuroanatomical heterogeneity and biological subtypes in children with ADHD

BackgroundNeuroimaging studies suggest substantial individual heterogeneity in brain phenotypes in attention-deficit/hyperactivity disorder (ADHD). However, how these individual-level brain phenotypes contribute to the identification of ADHD biotypes and whether these biotypes have different treatment outcomes and neurobiological underpinnings remain largely unknown. MethodsWe collected multisite, high-quality structural magnetic resonance imaging data from 1,006 children aged 6-14 years, including 351 children with ADHD and 655 typically developing children. Normative growth models of cortical thickness were established for 219 regions in the typically developing children. Individual-level deviations from these normal references were quantified and clustered to identify ADHD biotypes. We validated the replicability and generalizability of the ADHD biotypes using two independent datasets and evaluated the associations of the biotypes with symptomatic, cognitive, and gene expression profiles, as well as follow-up treatment outcomes. FindingsNo more than 10% of children with ADHD had extreme deviations in cortical thickness in a single region, suggesting high heterogeneity among individuals with ADHD. On the basis of the brain deviation maps, we discovered two robust ADHD biotypes, an infra-normal subtype with cortical thinning associated with ADHD symptoms and a supranormal subtype with cortical thickening associated with cognition. Patients with the infra-normal subtype responded better to methylphenidate than to atomoxetine, although both subtypes showed treatment efficacy. Brain deviations in the infra-normal subtype were explained by the expression levels of genes enriched in presynaptic and axonal development and polygenic risk of ADHD. InterpretationWe identified anatomically distinct, clinically valuable, and biologically informed ADHD subtypes, providing insight into the neurobiological basis of clinical heterogeneity and facilitating a personalized medication strategy for ADHD patients. Panel: Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSubstantial individual heterogeneity in brain phenotypes in attention-deficit/hyperactivity disorder (ADHD) motivates the need to discover homogeneous biotypes. We searched PubMed for research articles on ADHD biotypes using brain MRI published before December 1, 2023, using the search terms ((attention deficit hyperactivity disorder [Title/Abstract]) OR (ADHD [Title/Abstract])) AND ((subtypes [Title/Abstract]) OR (subgroups [Title/Abstract]) OR (subtyping [Title/Abstract])) AND ((MRI [Title/Abstract]) OR (neuroimaging [Title/Abstract]) OR (brain [Title/Abstract])) without language restrictions. Of the eight included studies, two identified ADHD biotypes using structural morphology, four used functional activity, and two used multimodal features. However, none of these studies considered the developmental effect of the brain phenotypes, examined treatment response, or investigated the genetic correlates of the biotypes. Added value of this studyThis study is the first to use individualized brain measures extracted from normative models to investigate ADHD biotypes in a large sample of more than 1,000 children. We identified two reproducible ADHD biotypes, characterized by distinct symptomatic, cognitive, and gene expression profiles, as well as differential treatment responses. This study advances our understanding of the neurobiological basis underlying the clinical heterogeneity of ADHD and highlights the critical need to discover ADHD biotypes using an unbiased and individualized approach. Implications of all the available evidenceThis study revealed remarkable neuroanatomical heterogeneity in ADHD patients and identified anatomically distinct, clinically valuable, and biologically informed ADHD biotypes. Our findings have potential value for the investigation of data-driven biotypes to evaluate treatment efficacy and facilitate personalized treatment. We also highlight the need for future studies to move beyond the understanding of ADHD solely based on the "average patient" perspective.

neuroscience↗

bioRxiv2024

A new group of LysM-RLKs involved in symbiotic signal perception and arbuscular mycorrhiza establishment

Lipo-chitooligosaccharides (LCO) and short-chain chitooligosaccharides (CO) are produced by arbuscular mycorrhizal fungi (AMF) and activate the plant symbiosis signalling pathway, which is essential for mycorrhiza formation. High affinity LCO receptors belonging to the LysM receptor-like kinase (LysM-RLK) phylogenetic group LYR-IA play a role in AM establishment, but no plant high affinity short-chain CO receptors have yet been identified. Here we studied members of the uncharacterized LYR-IB group, and found that they show high affinity for LCO, short- and long-chain CO, and play a complementary role with the LYR-IA LCO receptors for AM establishment. While LYR-IB knock out mutants had a reduced AMF colonization in several species, constitutive/ectopic expression in wheat increased AMF colonization. LYR-IB function is conserved in all tested angiosperms, but in most japonica rice a deletion creates a frameshift in the gene, explaining differences in AM phenotypes between rice and other monocot single LYR-IA mutants. In conclusion, we identified a class of LysM-RLK receptors in angiosperms with new biochemical properties and a role in both LCO and CO perception for AM establishment.

plant biology↗

bioRxiv2024

Mechanisms mediating arylidene-indolinones induced degradation: thoughts on "Discovery of a Drug-like, Natural Product-Inspired, DCAF11 Ligand Chemotype"

In the recent issue of Nature Communications (2023 Nov 30;14(1):7908), Xue et. al. reported a very interesting and significant discovery of a possible DCAF11 ligand chemotype that could be used as the "warhead" to design bifunctional compounds for targeted degradation via engaging the E3 ligase DCAF11 1 (annotated as ref 1 hereafter). The discovery is of importance to the targeted protein degradation field and was inspired by previous reports suggesting that similar compounds may also engage the autophagosome protein LC3 for degradation and function as autophagy-tethering compounds (ATTECs) 2, 3, 4, 5, 6, 7, which seem to be inconsistent with ref 1. We think that the conclusions based on these data are not necessarily mutually exclusive. After performing additional experiments and analyses, we would like to discuss some possibilities explaining such discrepancies and make a few points of clarification.

biochemistry↗

bioRxiv2024

DUAL: deep unsupervised simultaneous simulation and denoising for cryo-electron tomography

Recent biotechnological developments in cryo-electron tomography allow direct visualization of native sub-cellular structures with unprecedented details and provide essential information on protein functions/dysfunctions. Denoising can enhance the visualization of protein structures and distributions. Automatic annotation via data simulation can ameliorate the time-consuming manual labeling of large-scale datasets. Here, we combine the two major cryo-ET tasks together in DUAL, by a specific cyclic generative adversarial network with novel noise disentanglement. This enables end-to-end unsupervised learning that requires no labeled data for training. The denoising branch outperforms existing works and substantially improves downstream particle picking accuracy on benchmark datasets. The simulation branch provides learning-based cryo-ET simulation for the first time and generates synthetic tomograms indistinguishable from experimental ones. Through comprehensive evaluations, we showcase the effectiveness of DUAL in detecting macromolecular complexes across a wide range of molecular weights in experimental datasets. The versatility of DUAL is expected to empower cryo-ET researchers by improving visual interpretability, enhancing structural detection accuracy, expediting annotation processes, facilitating cross-domain model adaptability, and compensating for missing wedge artifacts. Our work represents a significant advancement in the unsupervised mining of protein structures in cryo-ET, offering a multifaceted tool that facilitates cryo-ET research.

bioinformatics↗

bioRxiv2024

Replicating enzymatic activity by positioning active sites with synthetic protein scaffolds

Evolutionary constraints significantly limit the diversity of naturally occurring enzymes, thereby reducing the sequence repertoire available for enzyme discovery and engineering. Recent breakthroughs in protein structure prediction and de novo design, powered by artificial intelligence, now enable us to create enzymes with desired functions without relying on traditional genome mining. Here, we demonstrate a computational strategy for creating new-to-nature PET hydrolases by leveraging the known catalytic mechanisms and implementing multiple deep learning algorithms and molecular computations. This strategy includes the extraction of functional motifs from a template enzyme (here we use leaf-branch compost cutinase, LCC), regeneration of new protein scaffolds, computational screening, experimental validation, and sequence refinement. We successfully replicate PET hydrolytic activity with designer enzymes that are at least 30% shorter in sequence length than LCC. Among them, RsPETase 1 stands out due to its robust expressibility. It exhibits comparable activity to IsPETase and considerable thermostability with a melting temperature of 56 {degrees}C, despite sharing only 34% sequence similarity with LCC. This work suggests that enzyme diversity can be expanded by recapitulating functional motifs with computationally built protein scaffolds, thus generating opportunities to acquire highly active and robust enzymes that do not exist in nature.

biochemistry↗

bioRxiv2024

Changes in the cellular makeup of motor patterning circuits drive courtship song evolution in Drosophila

How evolutionary changes in genes and neurons encode species variation in complex motor behaviors are largely unknown. Here, we develop genetic tools that permit a neural circuit comparison between the model species Drosophila melanogaster and the closely-related species D. yakuba, who has undergone a lineage-specific loss of sine song, one of the two major types of male courtship song in Drosophila. Neuroanatomical comparison of song patterning neurons called TN1 across the phylogeny demonstrates a link between the loss of sine song and a reduction both in the number of TN1 neurons and the neurites serving the sine circuit connectivity. Optogenetic activation confirms that TN1 neurons in D. yakuba have lost the ability to drive sine song, while maintaining the ability to drive the singing wing posture. Single-cell transcriptomic comparison shows that D. yakuba specifically lacks a cell type corresponding to TN1A neurons, the TN1 subtype that is essential for sine song. Genetic and developmental manipulation reveals a functional divergence of the sex determination gene doublesex in D. yakuba to reduce TN1 number by promoting apoptosis. Our work illustrates the contribution of motor patterning circuits and cell type changes in behavioral evolution, and uncovers the evolutionary lability of sex determination genes to reconfigure the cellular makeup of neural circuits.

evolutionary biology↗

bioRxiv2024

Unveiling the regulatory role of GRP7 in ABA signal-mediated mRNA translation efficiency regulation

Abscisic acid (ABA) is a crucial phytohormone involved in plant growth and stress responses. Although ABA has been implicated in the regulation of translation efficiency in Arabidopsis thaliana, the underlying mechanism remains largely unknown. In this study, we discovered that ABA treatment modulates globally translation efficiency (TE) by affecting pre-rRNA processing in the nucleolus and ribosome distribution status in the cytoplasm. The regulation of TE by ABA was largely abolished in mutants of ABA signaling core components, such as receptors PYRABACTIN RESISTANCE1/PYRABACTIN-LIKE/REGULATORY COMPONENTS OF ABA RECEPTORS (PYR/PYL/RACRs), the protein phosphatase 2Cs (PP2Cs), and the SNF1-related protein kinase 2s (SnRK2s). ABA treatment reduced the protein levels of glycine-rich RNA binding protein 7 (GRP7) in the signaling core components-dependent manner. Ribo-seq and CLIP-seq analyses unveiled GRP7s role in governing the TE of a substantial proportion of ABA-regulated genes, although independent of directly binding to the respective mRNAs. Furthermore, GRP7 directly bound to pre-rRNA and interacted with Ribosomal protein S6 (RPS6A), RPS14A and RPL36aA in the nucleolus to regulate rRNA processing. Additionally, GRP7 associated with mature polysome in the cytoplasm and is hypersensitive to translation inhibitor anisomycin when loss of function. Collectively, our study unveils the role of GRP7 in mediating translation regulation in ABA signaling, providing a novel regulatory model for plants to response to environmental stresses.

plant biology↗