Biology subjects

Whelan, J.

Publications and source records attributed to Whelan, J..

At least 19 recordsLinked to original sources

bioRxiv2026

iGEX: an interactive Gene EXpression exploration platform for the analysis of transcriptomic and proteomic datasets

High-throughput transcriptomic and proteomic studies have generated a rapidly expanding collection of publicly available datasets. However, extracting biological insight from these resources often requires researchers to repeatedly download, reformat, integrate and analyse individual files using specialised tools. This process is time-consuming and often requires coding expertise. Here, we present iGEX, an interactive exploration platform that can incorporate publicly available and user-generated transcriptomic and proteomic datasets into a single visual workspace to simplify the analysis of multiple transcripts and/or proteins across numerous datasets. iGEX enables researchers to select gene/protein targets and experiments and compare expression patterns across biological conditions and experiments. User-generated data can be examined alongside numerous public resources such as EMBL-EBI Expression Atlas, Bgee, and PaxDb to determine whether any observed patterns are evident across experiments, species or experimental contexts. Users can visualise and move directly between data tables, principal component analysis, expression and correlation heatmaps, hierarchical clustering and volcano plots, all of which are editable and downloadable.

bioinformatics↗

bioRxiv2026

A NOVEL MITOCHONDRIAL PEPTIDE ESSENTIAL FOR RESPIRATORY CAPACITY PROMOTES GROWTH, YIELD AND ABIOTIC STRESS TOLERANCE IN PLANTS

Efforts to boost crop productivity have focused on improving photosynthesis. However, plant respiration consumes over 90% of fixed carbon, fueling growth, stress responses, and resource acquisition. Despite its metabolic centrality, respiratory regulation remains underexplored as a yield target. Here, we identify AtMLSP1 (At4g17085), a 57-amino-acid mitochondrial inner membrane peptide in Arabidopsis thaliana. Loss-of-function atmlsp1 mutants show impaired growth, while AtMLSP1 overexpression boosts biomass, seed yield, and high light tolerance. No induction of alternative oxidase protein abundance or activity was observed in atmlsp1 plants, a response normally triggered by respiratory perturbation. Mitochondria isolated from atmlsp1 lines had an approximately 90% reduction in the amount of the intermembrane space protein Cytochrome c and a 30% reduction in all subunits of complex III, while other respiratory complexes remain unaffected. As expected, loss-of-function plants atmlsp1 reveal a significant decrease in total respiratory capacity and membrane potential, but mitochondrial integrity, and abundance of complex I, II and complex IV were unchanged. Overexpression of the orthologues of this gene in Oryza sativa (rice) and Glycine max (soybean) results in a significant increases in yield (seed number and size) under field conditions across different locations.

plant biology↗

bioRxiv2026

Mitochondrial Retrograde Signaling in Arabidopsis thaliana: heterogenous, spatial and polarised aspects

Organelle retrograde signaling studies have exclusively relied on bulk tissues, obscuring cell-type specificity, spatial organization, and heterogeneity within cell types. Here, we use single-nucleus and spatial RNA sequencing to define the cellular and spatial architecture of mitochondrial stress signaling in Arabidopsis thaliana. Inhibition of the mitochondrial electron transport chain by antimycin A and myxothiazol rapidly redistributed nuclei among transcriptional states within epidermal, leaf pavement, and mesophyll lineages, revealing that mitochondrial dysfunction reshapes cell identity trajectories rather than eliciting a uniform response. Stress-associated clusters were already present at low frequency in untreated samples, but the numbers of cells increased following stress treatments, indicating that stress increases the proportion of nuclei occupying pre-existing, primed transcriptional states. Gene-level analyses revealed distinct temporal dynamics and variable cell-state penetrance of the canonical mitochondrial stress markers and identified broadly responsive genes absent from earlier marker sets. Spatial transcriptomics resolved tissue-scale responses, spanning from pan-tissue induction to cell-type- and cluster-restricted activation, and uncovered pronounced adaxial-abaxial polarity in gene expression. Cell identity and spatial inferences were supported by extensive experimental validation using a custom 465-probe 10x Xenium panel and 52 promoter-GFP reporter lines. Together, these data provide a high-resolution framework for organelle-to-nucleus signaling and a resource of cell-type markers and spatial maps to dissect mitochondrial stress signaling and its integration with developmental and environmental pathways.

plant biology↗

bioRxiv2025

METABOLIC AND TRANSCRIPTOMIC ANALYSES IDENTIFY COORDINATED RESOURCE REALLOCATION IN RESPONSE TO PHOSPHATE SUPPLY IN HEMP

Cannabis sativa L., one of the earliest domesticated crops, was selectively bred into drug-type (high phytocannabinoid yield) and hemp-type (fibre and seed production) varieties, resulting in divergent traits including nutrient requirements. To address the limited molecular understanding of nutrient use regulation in Cannabis, this study investigated the response of dual-purpose hemp to varying phosphate availability. Physiological and transcriptomic profiling across source and sink organs revealed that biomass partitioning to flowers was sustained unless phosphate was completely withdrawn. Analyses of key phosphate-responsive genes highlighted the importance of P reallocation to flowers via glycolytic bypass reactions and release of phosphate from organic pools in source organs. Phospholipid biosynthesis and other P-dependent metabolic pathways remained active in sink organs. While the transcriptional response of key regulators, such as SPX DOMAIN GENE (SPX), PHOSPHATE STARVATION RESPONSE1 (PHR1) and NITRATE-INDUCIBLE, GARP-TYPE TRANSCRIPTIONAL REPRESSOR1 (NIGT1) followed canonical patterns, our data suggest a lack of suppression of phosphate uptake and root-to-shoot translocation at higher phosphate supply levels. Subsequent depletion of nitrate pools restricts further growth. These findings uncover conserved and unique aspects of nutrient signalling in hemp, shedding light on its adaptation to nutrient-poor soils through distinct source-sink regulation. HIGHLIGHTContrasting human selection in Cannabis sativa enables the analysis of divergent nutrient-use strategies. Our integrated transcriptomic and physiological data revealed adaptive resource allocation, informing the development of nutrient-efficient cultivars.

plant biology↗

bioRxiv2024

SoyOD: An Integrated Soybean Multi-omics Database for Mining Genes and Biological Research

Soybean is a globally important crop for food, feed, oil, and nitrogen fixation. A variety of multi-omics research has been carried out generating datasets ranging from genotype to phenotype. To utilise this data, a soybean multi-omics database that has broad data coverage and comprehensive data analysis tools would be of value for basic and applied research. We present the soybean omics database (SoyOD), which integrates significant new datasets with existing public datasets for the most comprehensive collection of soybean multi-omics information. Compared to the existing soybean database, SoyOD incorporates an extensive collection of novel data derived from the deep-sequencing of 984 germplasms, 162 novel transcriptome datasets from seeds at different developmental stages, 53 phenotypic datasets, and over 2500 phenotypic images. In addition, SoyOD integrates existing data resources, including 59 assembled genomes, genetic variation data from 3904 soybean accessions, 225 sets of phenotypic data, and 1097 transcriptomic sequences covering 507 different tissues and treatment conditions. SoyOD is a novel tool, as it can be used to mine and analyze candidate genes for important agronomic traits, as shown in a case study on plant height. Additionally, powerful analytical and easy-to-use toolkits enable users to easily access the available multi-omics datasets, and to rapidly search genotypic and phenotypic data in a particular germplasm. The novelty, comprehensiveness, and user-friendly features of SoyOD make it a valuable resource for soybean molecular breeding and biological research. SoyOD is publicly accessible at https://bis.zju.edu.cn/soyod.

plant biology↗

bioRxiv2023

Phosphate starvation regulates cellulose synthesis to modify root growth

In the model plant Arabidopsis thaliana, the absence of the essential macro-nutrient phosphate reduces primary root growth through decreased cell division and elongation, requiring alterations to the polysaccharide-rich cell wall surrounding the cells. Despite its significance, the regulation of cell wall synthesis in response to low phosphate levels is not well understood. In this study, we show that plants increase cellulose synthesis in roots under limiting phosphate conditions, which leads to changes in the thickness and structure of the cell wall. These changes contribute to the reduced growth of primary roots in low phosphate conditions. Furthermore, we found that the cellulose synthase complex activity at the plasma membrane increases during phosphate deficiency. Moreover, we show that this increase in the activity of the cellulose synthase complex is likely due to alterations in the phosphorylation status of cellulose synthases in low phosphate conditions. Specifically, phosphorylation of CELLULOSE SYNTHASE 1 at the S688 site decreases in low phosphate conditions. Phosphomimic versions of CELLULOSE SYNTHASE 1 with an S688E mutation showed significantly reduced cellulose induction and primary root length changes in low phosphate conditions. Protein structure modelling suggests that the phosphorylation status of S688 in CELLULOSE SYNTHASE 1 could play a role in stabilizing and activating the cellulose synthase complex. This mechanistic understanding of root growth regulation under limiting phosphate conditions provides potential strategies for changing root responses to soil phosphate content.

plant biology↗

bioRxiv2023

FTSH3 facilitates complex I degradation through a direct interaction with the complex I subunit PSST

Complex I (NADH dehydrogenase), the largest complex involved in mitochondrial oxidative phosphorylation is composed of nuclear and mitochondrial encoded subunits. Its assembly requires sequential addition of subdomains and modules. As it is prone to oxidative damage, complex I subunits continually undergo proteolysis and turnover. We describe the mechanism by which complex I abundance is regulated in a complex I deficient mutant. Using a forward genetic approach we have identified that the complex I Q-module domain subunit PSST, interacts with FTSH3 (Filamentous Temperature Sensitive H3) to mediate the disassembly of the matrix arm domain module for proteolysis and turnover as a means of protein quality control. We show the direct interaction of FTSH3 with PSST and identify the amino acid residues required for this interaction. It is the ATPase function of FTSH3 that is required for the interaction, as the mutation can be compensated by a proteolytically inactive form of FTSH3. Furthermore, it cannot be compensated by FTSH10 that is also located in mitochondria, as the latter does not interact with PSST. This study reveals the mechanistic process at the resolution of the residues involved of how FTSH3 recognises complex I for degradation.

plant biology↗

bioRxiv2023

Spatially Resolved Transcriptomic Analysis of the Germinating Barley Grain

Seeds, which provide a major source of calories for humans, are a unique stage of a flowering plant s lifecycle. During seed germination the embryo reactivates rapidly and goes through major developmental transitions to become a seedling. This requires extensive and complex spatiotemporal coordination of cell and tissue activity. Existing gene expression profiling methods, such as laser capture microdissection followed by RNA-seq and single-cell RNA-seq, suffer from either low throughput or the loss of spatial information about the cells analysed. Spatial transcriptomics methods couple high throughput analysis of gene expression simultaneously with the ability to record the spatial location of each individual region analysed. We developed a spatial transcriptomics workflow for germinating barley grain to better understand the spatiotemporal control of gene expression within individual seed cell types. More than 14,000 genes were differentially regulated across 0, 1, 3, 6 and 24 hours after imbibition. This approach enabled us to observe that many functional categories displayed specific spatial expression patterns that could be resolved at a sub-tissue level. Individual aquaporin gene family members, important for water and ion transport, had specific spatial expression patterns over time, as well as genes related to cell wall modification, membrane transport and transcription factors. Using spatial autocorrelation algorithms, we were able to identify auxin transport genes that had increasingly focused expression within subdomains of the embryo over germination time, suggestive of a role in establishment of the embryo axis. Together, our data provides an unprecedented spatially resolved cellular map for barley grain germination and specific genes to target for functional genomics to define cellular restricted processes in tissues during germination. The data can be viewed at https://spatial.latrobe.edu.au/.

plant biology↗

bioRxiv2023

Establishment of cell transcriptional identity during seed germination

Germination involves highly dynamic transcriptional programs as the cells of seeds reactivate and express the functions necessary to establish in the environment. Individual cell types have distinct roles within the embryo, so must therefore have cell-type specific gene expression and gene regulatory networks. We can better understand how the functions of different cell types are established and contribute to the embryo by determining how cell-type specific transcription begins and changes through germination. Here we describe a temporal analysis of the germinating Arabidopsis embryo at single-cell resolution. We define the highly dynamic cell-type specific patterns of gene expression and how these relate to changing cellular function as germination progresses. Underlying these are unique gene regulatory networks and transcription factor activity. We unexpectedly discover that most embryo cells transition through the same initial transcriptional state early in germination, after which cell-type specific gene expression is established. Furthermore, our analyses support previous findings that the earliest events leading to the induction of embryo growth take place in the vasculature. Overall, our study constitutes a general framework to characterise Arabidopsis cell states through embryo growth, allowing investigation of different genotypes and other plant species whose seed strategies may differ.

plant biology↗

bioRxiv2022

An environmentally-responsive transcriptional state modulates cell identities during root development

Roots are fundamental organs for plant development and response to their environment: they anchor the plant to its growth substrate, uptake nutrients and water vital to plant growth, and can sense and respond to a variety of biotic and abiotic stresses. The architecture of root systems and their growth are known to be strongly affected by the environmental conditions found in the soil. However, the acquisition of cell identities at the root meristem is still mainly viewed as ontogenetically driven, where a small number of stem cells generate all the cell types through stereotyped divisions followed by differentiation, along a simple developmental trajectory. The extent to which environmental cues precisely shape and affect these developmental trajectories remains an open question. We used single-cell RNA-seq, combined with spatial mapping, to deeply explore the trajectories of cell states at the tip of Arabidopsis roots, known to contain multiple developing lineages. Surprisingly, we found that most lineage trajectories exhibit a stereotyped bifid topology with two developmental trajectories rather than one. The formation of one of the trajectories is driven by a strong and specific activation of genes involved in the responses to various environmental stimuli, that affects only of a subset of the cells in multiple cell types simultaneously, revealing another layer of patterning of cell identities in the root that is independent of cell ontogeny. We demonstrate the robustness of this environmentally responsive transcriptional state by showing that it is present in a mutant where cell type identities are greatly perturbed, as well as in different Arabidopsis ecotypes. We also show that the root can adapt the proportion of cells that acquire this particular state in response to environmental signals such as nutrient availability. The discovery of this cell state reveals new layers of cell identity that may underpin the adaptive potential of plant development.

plant biology↗

bioRxiv2022

ColorBayes: Improved color correction of high-throughput plant phenotyping images to account for local illumination differences

BackgroundColor distortion is an inherent problem in image-based phenotyping systems that are illuminated by artificial light. This distortion is problematic when examining plants because it can cause data to be incorrectly interpreted. One of the leading causes of color distortion is the non-uniform spectral and spatial distribution of artificial light. However, color correction algorithms currently used in plant phenotyping assume that a single and uniform illuminant causes color distortion. These algorithms are consequently inadequate to correct the local color distortion caused by multiple illuminants common in plant phenotyping systems, such as fluorescent tubes and LED light arrays. We describe here a color constancy algorithm, ColorBayes, based on Bayesian inference that corrects local color distortions. The algorithm estimates the local illuminants using the Bayes rule, the maximum a posteriori, the observed image data, and prior illuminant information. The prior is obtained from light measurements and Macbeth ColorChecker charts located on the scene. ResultsThe ColorBayes algorithm improved the accuracy of plant color on images taken by an indoor plant phenotyping system. Compared with existing approaches, it gave the most accurate metric results when correcting images from a dataset of Arabidopsis thaliana images. The software is available at https://github.com/diloc/Color_correction.git.

plant biology↗

bioRxiv2021

Single Cell App: An App for Single Cell RNA-sequencing Data Visualization, Comparison and Discovery

The Single Cell App is a cloud-based application that allows visualisation and comparison of scRNA-seq data and is scalable according to use. Users upload their own or publicly available scRNA-seq datasets after pre-processing to be visualised using a web browser. The data can be viewed in two colour modes, Cluster - representing cell identity, and Values - level of expression, and data queried using keyword or gene identification number(s). Using the app to compare four different studies we determined that some genes frequently used as cell-type markers are in fact study specific. Phosphate transporter and hormone response genes were exemplary investigated with the app. This showed that the apparent cell specific expression of PHO1;H3 differed between GFP-tagging and scRNA-seq studies. Some phosphate transporter genes were induced by protoplasting, they retained cell specificity, indicating that cell specific stress responses (i.e. protoplasting). Examination of the cell specificity of hormone response genes revealed that 132 hormone responsive genes display restricted expression and that the jasmonate response gene TIFY8 is expressed in endodermal cells which differs from previous reports. It also appears that JAZ repressors have cell-type specific functions. These differences, identified using the Single Cell App, highlight the need for resources to enable researchers to find common and different patterns of cell specific gene expression. Thus, the Single Cell App enables researchers to form new hypothesis, perform comparative studies, allows for easy re-use of data for this emerging technology to provide novel avenues to crop improvement.

plant biology↗

bioRxiv2021

GmSALT3 expression improves reactive oxygen species detoxification in salt-stressed soybean roots

Soybean plants are salinity (NaCl) sensitive, with their yield significantly decreased under moderately saline conditions. GmSALT3 is the dominant gene underlying a major QTL for salt tolerance in soybean. GmSALT3 encodes a transmembrane protein belonging to the plant cation/proton exchanger (CHX) family. It is currently unknown through which molecular mechanism(s) the ER-localised GmSALT3 contributes to salinity tolerance, as its localisation excludes direct involvement in ion exclusion. In order to gain insights into potential molecular mechanism(s), we used RNA-seq analysis of roots from two soybean NILs (Near Isogenic Lines); NIL-S (salt-sensitive, Gmsalt3) and NIL-T (salt-tolerant, GmSALT3), grown under control and saline conditions (200 mM NaCl) at three time points (0h, 6h, and 3 days). Gene ontology (GO) analysis showed that NIL-T has greater responses aligned to oxidation reduction. ROS were shown less abundant and scavenging enzyme activity was higher in NIL-T, consistent with the RNA-seq data. Further analysis indicated that genes related to calcium signalling, vesicle trafficking and Casparian strip (CS) development were upregulated in NIL-T following salt treatment. We propose that GmSALT3 improves the ability of NIL-T to cope with saline stress through preventing ROS overaccumulation in roots, and potentially modulating Ca2+ signalling, vesicle trafficking and formation of diffusion barriers. HighlightRNA-seq analysis revealed that GmSALT3, which confers improved salt tolerance on soybean, improves reactive oxygen species detoxification in roots.

plant biology↗

bioRxiv2021

RNA labelling in live plants reveals single cell transcriptional dynamics: application to phosphate signaling

Plants are sessile organisms constantly adapting to ambient fluctuations through spatial and temporal transcriptional responses. Here, we implemented the latest generation RNA imaging system and combined it with microfluidics to visualize transcriptional regulation in living Arabidopsis plants. This enabled quantitative measurements of the transcriptional activity of single loci in single cells, real time and changing environmental conditions. Using phosphate responsive genes as model, we found that active genes displayed high transcription initiation rates ([~]3s) and frequently clustered together in endoreplicated cells. We observed gene bursting and large allelic differences in single cells, revealing that at steady-state, intrinsic noise dominated extrinsic variations. Moreover, we established that transcriptional repression triggered in roots by phosphate, a crucial macronutrient limiting plant development, occurred with unexpected fast kinetics ([~]minutes) and striking heterogeneity between neighboring cells. Access to single cell RNA polymerase II dynamics within live plants will benefit future studies of signaling processes.

plant biology↗

bioRxiv2020

RNA-seq analysis of laser micro-dissected Arabidopsis thaliana leaf epidermis, mesophyll and vasculature defines tissue-specific transcriptional responses to multiple stress treatments

Acclimation of plants to adverse environmental conditions requires the coordination of gene expression and signalling pathways between tissues and cell types. As the energy and carbon capturing organs, leaves are significantly affected by abiotic and biotic stresses. However, tissue- or cell type-specific analyses of stress responses have largely focussed on the Arabidopsis root. Here, we comparatively explore the transcriptomes of three leaf tissues (epidermis, mesophyll, vasculature) after induction of diverse stress pathways by chemical stimuli (antimycin A, 3-amino-1,2,4-triazole, methyl viologen, salicylic acid) and UV light in Arabidopsis. Profiling stimuli-dependent changes after treatments revealed an overall reduction in the tissue-specific expression of genes, with only a limited number gaining or changing their tissue-specificity. We find no evidence of a common stress response, with only a few genes responsive to two or more treatments in the analysed tissues. However, differentially expressed genes overlap across tissues for individual treatments. Further analyses provided evidence for an interaction of auxin and ethylene that mediates retrograde signalling during mitochondrial dysfunction specifically in the epidermis, and a gene regulatory network defined the hierarchy of interactions. Taken together, we generated an extensive reference data set and results enable the tailoring of the tissue-specific engineering of stress tolerant plants.

plant biology↗

bioRxiv2020

Identification of a unique ZIP transporter involved in zinc uptake via the arbuscular mycorrhizal fungal pathway

Low soil zinc (Zn) availability is a limiting factor for crop yield, and increasing Zn content is a major target for the biofortification of major crops. Arbuscular mycorrhizal (AM) fungi associate with the roots of most terrestrial plant species and improve the host plants growth and nutrition through the mycorrhizal pathway of nutrient uptake. Although the physiology of Zn uptake through the mycorrhizal pathway is well established, the identity of the molecular components responsible for Zn transport in the mycorrhizal pathway are unknown. RNA-seq analysis identified the putative Zn transporter gene MtZIP14 by its marked up-regulation in Medicago truncatula roots when colonised by the AM fungus Rhizophagus irregularis under varying soil Zn supply. Expression of GFP-tagged MtZIP14 in roots revealed that it is exclusively localised to the site of plant-fungal nutrient exchange in cortical cells, the peri-arbuscular membrane. Expression of MtZIP14 in a yeast mutant lacking Zn transport function restored growth under low Zn availability. M. truncatula MtZIP14 loss-of-function mutants had reduced shoot biomass compared to the wild-type when colonised by AM fungi and grown under low Zn. Vesicular and arbuscular colonisation, but not hyphal colonisation, were also lower in mtzip14 mutant plants. Based on these results we propose that MtZIP14 plays a key role in the transport of Zn from AM fungus to plant across the peri-arbuscular membrane, and MtZIP14 function is crucial to plant competitiveness in a low Zn soil. Significance statementMajority of crop plant species associate with arbuscular mycorrhizal fungi, which can increase plant nutrient uptake. Improving our knowledge of how Zn is taken up in mycorrhizal plants will lead to improved plant and human Zn nutrition outcomes. Here, we report a novel plant transporter with a major role in Zn nutrition of mycorrhizal plants. MtZIP14 is involved in Zn transport, is exclusively localised to the specialised plant-fungal interface in roots, and impairment of MtZIP14 gene function results in negative impacts on both plant growth and Zn nutrition.

plant biology↗

bioRxiv2020

SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial derived cells and cardiomyocytes

Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which the recently emerged SARS-CoV-2 activates or antagonizes these pathways is relatively unknown. We found that SARS-CoV-2 infects patient-derived nasal epithelial cells, present at the initial site of infection, induced pluripotent stem cell-derived alveolar type 2 cells (iAT2), the major cell type infected in the lung, and cardiomyocytes (iCM), consistent with cardiovascular consequences of COVID-19 disease. Robust activation of IFN or OAS-RNase L is not observed in these cell types, while PKR activation is evident in iAT2 and iCM. In SARS-CoV-2 infected Calu-3 and A549ACE2 lung-derived cell lines, IFN induction remains relatively weak; however activation of OAS-RNase L and PKR is observed. This is in contrast to MERS-CoV, which effectively inhibits IFN signaling as well as OAS-RNase L and PKR pathways, but similar to mutant MERS-CoV lacking innate immune antagonists. Remarkably, both OAS-RNase L and PKR are activated in MAVS knockout A549ACE2 cells, demonstrating that SARS-CoV-2 can induce these host antiviral pathways despite minimal IFN production. Moreover, increased replication and cytopathic effect in RNASEL knockout A549ACE2 cells implicates OAS-RNase L in restricting SARS-CoV-2. Finally, while SARS-CoV-2 fails to antagonize these host defense pathways, which contrasts with other coronaviruses, the IFN signaling response is generally weak. These host-virus interactions may contribute to the unique pathogenesis of SARS-CoV-2. SignificanceSARS-CoV-2 emergence in late 2019 led to the COVID-19 pandemic that has had devastating effects on human health and the economy. Early innate immune responses are essential for protection against virus invasion. While inadequate innate immune responses are associated with severe COVID-19 diseases, understanding of the interaction of SARS-CoV-2 with host antiviral pathways is minimal. We have characterized the innate immune response to SARS-CoV-2 infections in relevant respiratory tract derived cells and cardiomyocytes and found that SARS-CoV-2 activates two antiviral pathways, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR), while inducing minimal levels of interferon. This in contrast to MERS-CoV which inhibits all three pathways. Activation of these pathways may contribute to the distinctive pathogenesis of SARS-CoV-2.

microbiology↗

bioRxiv2020

The genetic origin of evolidine, the first cyclopeptide discovered in plants, and related orbitides

Cyclic peptides are reported to have antibacterial, antifungal and other bioactivities. Several genera of the Rutaceae family are known to produce orbitides, which are small head-to-tail cyclic peptides composed of proteinogenic amino acids and lacking disulfide bonds. Melicope xanthoxyloides is an Australian rain forest tree of the Rutaceae family in which evolidine - the first plant cyclic peptide - was discovered. Evolidine (cyclo-SFLPVNL) has subsequently been all but forgotten in the academic literature, but here we use tandem mass spectrometry to rediscover evolidine and using de novo transcriptomics we show its biosynthetic origin to be from a short precursor just 48 residues in length. In all, seven M. xanthoxyloides orbitides were found and they had atypically diverse C-termini consisting of residues not recognized by either of the known proteases plants use to macrocyclize peptides. Two of the novel orbitides were studied by nuclear magnetic resonance spectroscopy and although one had definable structure, the other did not. By mining RNA-seq and whole genome sequencing data from other species, it was apparent that a large and diverse family of peptides is encoded by sequences like these across the Rutaceae.

biochemistry↗