Biology subjects

von Arnim, A. G.

Publications and source records attributed to von Arnim, A. G..

5 recordsLinked to original sources

bioRxiv2023

A phosphorylation-deficient ribosomal protein eS6 is largely functional in Arabidopsis thaliana, rescuing mutant defects from global translation and gene expression to photosynthesis and growth

The eukaryote-specific ribosomal protein of the small subunit eS6 is phosphorylated through the Target of rapamycin (TOR) kinase pathway. Although this phosphorylation event responds dynamically to environmental conditions and has been studied for over 50 years, its biochemical and physiological significance remains controversial and poorly understood. Here we report data from Arabidopsis thaliana, which indicate that plants expressing only a largely phospho-deficient isoform of eS6 grow essentially normally under laboratory conditions. The eS6A (RPS6A) paralog of eS6 functionally rescued double mutations in both rps6a and rps6b genes when expressed at approximately twice the wild-type dosage. A mutant isoform of eS6A lacking the major six phosphorylatable serine and threonine residues in its carboxyl-terminal tail also rescued the lethality, rosette growth, and polyribosome loading of the double mutant. It also complemented many mutant phenotypes of rps6 that were newly characterized here, including photosynthetic efficiency, and the vast majority of gene expression defects that were measured by transcriptomics and proteomics. However, compared to plants rescued with a phospho-enabled version of eS6A, the phospho-deficient seedlings retained a mild pointed-leaf phenotype, root growth was reduced, and certain cell cycle related mRNAs and ribosome biogenesis proteins were misexpressed. The residual defects of the phospho-deficient seedlings could be understood as an incomplete rescue of the rps6 mutant defects, with little or no evidence for gain-of-function defects. As expected, the phospho-deficient eS6A also rescued the rps6a and rps6b single mutants; however, phosphorylation of the eS6B paralog remained lower than predicted, further underscoring that plants can tolerate phospho-deficiency of eS6 well. Our data also yield new insights into how plants cope with mutations in essential, duplicated ribosomal protein isoforms.

plant biology↗

bioRxiv2021

Enhancing Quantitative and Data Science Education for Graduate Students in Biomedical Science

Substantial guidance is available on undergraduate quantitative training for biologists, including reports focused on biomedical science, but far less attention has been paid to the graduate curriculum. In this setting, we propose an innovative approach to quantitative education that goes beyond recommendations of a course or set of courses or activities. Due to the diversity of quantitative methods, it is infeasible to expect that biomedical PhD students can be exposed to more than a minority of the quantitative concepts and techniques employed in modern biology. We developed a novel prioritization approach in which we mined and analyzed quantitative concepts and skills from publications that faculty in relevant units deemed central to the scientific comprehension of their field. The analysis provides a prioritization of quantitative skills and concepts and could represent an effective method to drive curricular focus based upon program-specific faculty input for biological science programs of all types. Our results highlight the disconnect between typical undergraduate quantitative education for life science students, focused on continuous mathematics, and the concepts and skills in graphics, statistics, and discrete mathematics that arise from priorities established by biomedical science faculty. One Sentence SummaryWe developed a novel approach to prioritize quantitative concepts and methods for inclusion in a graduate biomedical science curriculum based upon approaches included in faculty-identified key publications.

scientific communication and education↗

bioRxiv2020

Early detection of daylength variations with a feedforward circuit co-regulated by circadian rhythm and diel light-dark cycle

Light-entrained circadian clocks confer rhythmic dynamics of cellular and molecular activities to animals and plants. These intrinsic clocks allow stable anticipations to light-dark (diel) cycles. Many genes in the model plant Arabidopsis thaliana are regulated by diel cycles via pathways independent of the clock, suggesting that the integration of circadian and light signals is important for the fitness of plants. Previous studies of light-clock signal integrations have focused on moderate phase adjustment of the two signals. However, dynamical features of integrations across a broad range of phases remain elusive. We recently found that phosphorylation of RIBOSOMAL PROTEIN OF THE SMALL SUBUNIT 6 (RPS6 or eS6), a ubiquitous post-translational modification across kingdoms, is influenced by the circadian clock and the light-dark (diel) cycle in an opposite manner. In order to understand this striking phenomenon and its underlying information processing capabilities, we built a mathematical model for the eS6-P control circuit. We found that the dynamics of eS6-P can be explained by a feedforward circuit with inputs from both circadian and diel cycles. Furthermore, the early-day response of this circuit with dual rhythmic inputs is sensitive to the changes in daylength, including both transient and gradual changes observed in realistic light intervals across a year, due to weather and seasons. By analyzing published gene expression data, we found that the dynamics produced by the eS6-P control circuit can be observed in the expression profiles of a large number of genes. Our work provides mechanistic insights into the complex dynamics of a ribosomal protein, and it proposes a previously underappreciated function of the circadian clock which not only prepares organisms for normal diel cycles but also helps to detect both transient and seasonal changes with a predictive power.

systems biology↗

bioRxiv2019

Light dependent activation of the GCN2 kinase under cold and salt stress is mediated by the photosynthetic status of the chloroplast

Regulation of cytosolic mRNA translation is a key node for rapid adaptation to environmental stress conditions. In yeast and animals, phosphorylation of the -subunit of eukaryotic translation initiation factor eIF2 is the most thoroughly characterized event in regulating global translation under stress. In plants, the GCN2 kinase (General Control Non-derepressible-2) is the only known kinase for eIF2. GCN2 is activated under a variety of stresses including reactive oxygen species. Here we provide new evidence that the GCN2 kinase in Arabidopsis is also activated rapidly and in a light dependent manner by cold and salt treatments. These treatments alone did not repress global mRNA ribosome loading in a major way. The activation of GCN2 was attenuated by inhibitors of photosynthesis and antioxidants, suggesting that it is gated by the redox poise or the reactive oxygen status of the chloroplast. In keeping with these results, gcn2 mutant seedlings were more sensitive than wild type to both cold and salt in a root elongation assay. These data suggest that cold and salt stress may both affect the status of the cytosolic translation apparatus via the conserved GCN2-eIF2 module. The potential role of the GCN2 kinase pathway in the global repression of translation under abiotic stress will be discussed.

plant biology↗

bioRxiv2019

Light activates the translational regulatory GCN2 kinase via reactive oxygen species emanating from the chloroplast

Cytosolic mRNA translation is subject to global and mRNA-specific controls. Phosphorylation of translation initiation factor eIF2 anchors a reversible switch that represses translation globally. The stress-responsive GCN2 kinase is the only known kinase for eIF2 in Arabidopsis. Here we show that conditions that generate reactive oxygen species (ROS) in the chloroplast, such as dark-light transitions, high light, and the herbicide methyl viologen all rapidly activated the GCN2 kinase, whereas mitochondrial and ER stress did not. In addition, GCN2 activation was light dependent and mitigated by photosynthesis inhibitors and ROS quenchers. Accordingly, seedling growth of multiple gcn2 mutant alleles was retarded under conditions of excess light, implicating the GCN2-eIF2 pathway in responses to light and associated ROS. Once activated, the GCN2 kinase preferentially suppressed the ribosome loading of mRNAs for functions such as mitochondrial ATP synthesis, the chloroplast thylakoids, vesicle trafficking, and translation. The transcriptome of gcn2 mutants was sensitized to abiotic stress, including oxidative stress, as well as innate immune responses. Accordingly, gcn2 displayed defects in immune priming by the fungal elicitor, chitin. In conclusion, we provide evidence that reactive oxygen species produced by the photosynthetic apparatus help to activate the highly conserved GCN2 kinase, leading to eIF2 phosphorylation and thus affecting the status of the cytosolic protein synthesis apparatus.

plant biology↗