Biology subjects

McNally, K. L.

Publications and source records attributed to McNally, K. L..

10 recordsLinked to original sources

bioRxiv2026

Epigenetic regulation of DPP4 receptor expression by NONO enables replication of MERS-CoV

Middle East respiratory syndrome coronavirus (MERS-CoV), first reported in 2012, belongs to the Betacoronavirus genus, including SARS-CoV and SARS-CoV-2. Human-to-human transmission of MERS-CoV appears inefficient, but repeated spillover events have been reported from at least 27 countries, raising concern for future emergent events. Coronaviruses (CoVs) rely extensively on host proteins to support their replication. Several studies have implicated the paraspeckle non-POU domain-containing octamer-binding protein (NONO) as an RNA-binding protein (RBP) that binds to CoV genomes, but the role of this protein in regulating replication is unknown. Here, we show that NONO is required for expression of dipeptidyl peptidase 4 (DPP4, also known as CD26), the major cellular receptor required for MERS-CoV attachment and entry. NONO did not impact DPP4 mRNA processing or stability but instead promoted DPP4 transcription through control of active H3K4me3 and repressive H3K27me3 histone modifications at the DPP4 locus. Together, these findings identify NONO as a key proviral host factor for MERS-CoV and reveal an epigenetic mechanism linking a host RBP to viral entry receptor expression that may represent a target for therapeutic strategies.

microbiology↗

bioRxiv2026

Restraint of Powassan virus replication by TRIM5α facilitates viral avoidance of antiviral immunity

TRIpartite Motif (TRIM) protein 5 alpha (TRIM5) is a well characterized cellular inhibitor of lentivirus replication that limits transmission of related viruses between primates. We previously reported that TRIM5 derived from humans and rhesus macaques inhibits replication of orthoflaviviruses belonging to the tick-borne encephalitis virus (TBEV) serocomplex, including TBEV, Kyasanur forest disease virus and Langat virus (LGTV), but interestingly not the tick-borne Powassan virus (POWV). To further characterize the primate TRIM5 and orthoflavivirus interface, we screened TRIM5 variants from representative old- and new-world primates for restriction capacity. TRIM5 from old-world African green monkey, De Brazzas monkey and chimpanzee demonstrated virus-specific restriction of tick-borne orthoflaviviruses. Efforts to determine why TRIM5 fails to inhibit POWV revealed that our lab stock had acquired a non-synonymous mutation in NS3 that, when introduced into a POWV molecular clone, facilitated virus replication in the presence of all inhibitory primate TRIM5 proteins. Infection of human dendritic cells with TRIM5-resistant POWV resulted in high early replication and strong induction of interferon responses that limited replication compared with the wild-type virus. Thus, primate TRIM5 functions as a potent cellular barrier to infection with tick-borne orthoflaviviruses that restrains replication to a level that may help avoid early innate immune recognition.

microbiology↗

bioRxiv2025

A pan-gene catalogue of Asian cultivated rice

The rice genome underpins fundamental research and breeding, but the Nipponbare (japonica) reference does not fully encompass the genetic diversity of Asian rice. To address this gap, the Rice Population Reference Panel (RPRP) was developed, comprising high-quality assemblies of 16 rice cultivars to represent japonica, indica, aus, and aromatic varietal groups. The RPRP has been consistently annotated, supported by extensive experimental data and here we report the computational assignment, characterization and dissemination of stably identified pan-genes. We identified 25,178 core pan-genes shared across all cultivars, alongside cultivar-specific and family-enriched genes. Core genes exhibit higher gene expression and proteomic evidence, higher confidence protein domains and AlphaFold structures, while cultivar-specific genes were enriched for domains under selective breeding pressure, such as for disease resistance. This resource, integrated into public databases, enables researchers to explore genetic and functional diversity via a population-aware "reference guide" across rice genomes, advancing both basic and applied research.

genomics↗

bioRxiv2024

Novel Mechanism of Inflammatory Activation by Ebola Virus Matrix Protein Linked to the Ebolavirus Virulence

Uncontrolled systemic inflammatory responses are a critical pathological feature of fatal Ebola virus (EBOV) infection. While some inflammatory responses may originate from mononuclear phagocytes (MNPs), non-immune cells vastly outnumber MNPs and may be an important source of inflammation. Here, we demonstrated that highly virulent EBOV induced a high and sustained pro-inflammatory response compared to less virulent ebolaviruses in non-MNPs through TLR4-independent NF-{kappa}B activation. We identified the EBOV matrix protein VP40 as a potent activator of NF-{kappa}B in non-MNPs, whose intrinsic inflammatory activation ability is higher than VP40 proteins from less virulent ebolaviruses. This suggests that VP40 is a novel virulence determinant inducing distinct degrees of pro-inflammatory responses among ebolaviruses. Mechanistically, VP40 activated the NF-{kappa}B signaling pathway, primarily via TNFR1 using a ligand-independent mechanism. These findings reveal mechanisms that may drive systemic inflammation and promote EBOV pathogenesis, suggesting potential therapeutic strategies to mitigate immune dysregulation in severe EBOV infections.

microbiology↗

bioRxiv2024

Oryza genome evolution through a tetraploid lens

Oryza is remarkable genus - with two domesticated (i.e. Asian and African rice) and 25 diploid and tetraploid wild species, 11 extant genome types, and a [~]3.4-fold genome size variation - that possesses a virtually untapped reservoir of genes that can be used for crop improvement. Here we unveil and interrogate 11 new chromosome-level assemblies of nine tetraploid and two diploid wild Oryza species in the context of [~]15 million years of evolution of the genus. We show that the core Oryza (sub)genome across all genome types is only [~]200 Mb and largely syntenic, while the remaining nuclear fractions, spanning [~]80-600 Mb, are intermingled, extremely plastic and rapidly evolving. For the halophyte O. coarctata, we show that - despite the detection of gene fractionation in the subgenomes - homoeologous genes are expressed at higher levels in one subgenome over the other in a mosaic form, thereby showing subgenome equivalence. The integration of these 11 new ultra-high quality reference genomes with our previously published genome data sets provide a nearly complete picture of the consequences of natural and artificial selection across the evolutionary history of Oryza. This in turn opens the door to unlock their genetic potential for future crop improvement and neodomestication.

genomics↗

bioRxiv2023

HPC-based genome variant calling workflow (HPC-GVCW)

A high-performance computing genome variant calling workflow was designed to run GATK on HPC platforms. This workflow efficiently called an average of 27.3 M, 32.6 M, 168.9 M, and 16.2 M SNPs for rice, sorghum, maize, and soybean, respectively, on the most recently released high-quality reference sequences. Analysis of a rice pan-genome reference panel revealed 2.1 M novel SNPs that have yet to be publicly released.

genomics↗

bioRxiv2023

Rice Gene Index (RGI): a comprehensive pan-genome database for comparative and functional genomics of Asian rice

To integrate the genomic information of the rice pan-genome, we performed comparative analyses and established a user-friendly Rice Gene Index (RGI, https://riceome.hzau.edu.cn) platform with 16 platinum standard reference genomes and supplementary transcriptome data. To logically organize and scientifically the index of 744,233 genes among rice accessions, we detected 112,658 Ortholog Gene Indices, and provide GeneCard pages to query genomic, transcriptomic, and homology information for each gene. The RGI allows users to search for relationships and comprehensive information of genes in keyword-based, sequence-based, and relationship-based ways. Furthermore, users can visualize these relationships at local and global scales corresponding to Microcollinearity and Macrocollinearity modules.

genomics↗

bioRxiv2022

Identification of the rice Rc gene as a main regulator of seed survival under dry storage conditions

Seed deterioration during storage results in poor germination, reduced seed vigor, and non-uniform seedling emergence. The rate of aging depends on storage conditions (RH, temperature, and oxygen) and genetic factors. This study aims to identify these genetic factors determining the longevity of rice seeds stored under experimental aging conditions mimicking long-term dry storage. Genetic variation for tolerance to aging was studied in 300 Indica rice accessions and storing dry seeds under elevated partial pressure of oxygen (EPPO) condition, using a genome-wide association study. The association analysis yielded eleven unique regions across the genome for all measured germination parameters after aging. These genomic regions differed from regions previously identified in rice under humid experimental aging conditions. The significant single nucleotide polymorphism in the most prominent region was located within the Rc gene, encoding a bHLH transcription factor. Storage experiments using isogenic rice lines (SD7-1D (Rc) and SD7-1d (rc)) with the same allelic variation confirmed the functional role of the Rc gene, conferring a stronger tolerance to dry EPPO aging. A functional Rc gene results in the accumulation of pro-anthocyanidins in the pericarp of rice seeds, an important sub-class of flavonoids having strong antioxidant activity, which may explain why genotypes with an allelic variation for this gene show variation in seed tolerance to dry EPPO aging.

plant biology↗

bioRxiv2021

Mitophagy antagonism by Zika virus reveals Ajuba as a regulator of PINK1-Parkin signaling, PKR-dependent inflammation, and viral invasion of tissues.

Dysregulated inflammation dominated by chemokine expression is a key feature of disease following infection with the globally important human pathogens, Zika virus (ZIKV) and dengue virus, but a mechanistic understanding of how pro-inflammatory responses are initiated is lacking. Mitophagy is a quality control mechanism that regulates innate immune signaling and cytokine production through selective degradation of damaged mitochondria. Here, we demonstrate that ZIKV NS5 antagonizes mitophagy by binding to the host protein Ajuba and preventing its translocation to depolarized mitochondria where it is required for PINK1 activation and downstream signaling. Consequent mitophagy suppression amplified the production of pro-inflammatory chemokines through PKR sensing of mitochondrial RNA. In Ajuba-/- mice, ZIKV induced early expression of pro-inflammatory chemokines associated with significantly enhanced dissemination to tissues. This work identifies Ajuba as a critical regulator of mitophagy, and demonstrates a role for mitophagy in limiting systemic inflammation following infection by globally important human viruses.

microbiology↗

bioRxiv2019

Predicting agronomic traits and associated genomic regions in diverse rice landraces using marker stability

To secure the worlds food supply it is essential that we improve our knowledge of the genetic underpinnings of complex agronomic traits. In this paper, we report our findings from performing trait prediction and association mapping using marker stability in diverse rice landraces. We used the least absolute shrinkage and selection operator as our marker selection algorithm, and considered twelve real agronomic traits and a hundred simulated traits using a population with approximately a hundred thousand markers. For trait prediction, we considered several statistical/machine learning methods. We found that some of the methods considered performed best when preselected markers using marker stability were used. However, our results also show that one might need to make a trade-off between model size and performance for some learning methods. For association mapping, we compared marker stability to the genome-wide efficient mixed-model analysis (GEMMA), and for the simulated traits, we found that marker stability significantly outperforms GEMMA. For the real traits, marker stability successfully identifies multiple associated markers, which often entail those selected by GEMMA. Further analysis of the markers selected for the real traits using marker stability showed that they are located in known quantitative trait loci (QTL) using the QTL Annotation Rice Online database. Furthermore, co-functional network prediction of the selected markers using RiceNet v2 also showed association to known controlling genes. We argue that a wide adoption of the marker stability approach for the prediction of agronomic traits and association mapping could improve global rice breeding efforts.

bioinformatics↗