A Rab6 to Rab11 transition is required for dense-core granule and exosome biogenesis in < i > Drosophila < /i > secondary cells
by Adam Wells, Cl áudia C. Mendes, Felix Castellanos, Phoebe Mountain, Tia Wright, S. Mark Wainwright, M. Irina Stefana, Adrian L. Harris, Deborah C. I. Goberdhan, Clive Wilson
Secretory cells in glands and the nervous system frequently package and store proteins destined for regulated secretion in dense-core granules (DCGs), which disperse when released from the cell surface. Despite the relevance of this dynamic process to diseases such as diabetes and human neurodegenerative disorders, our mechanistic understanding is relatively limited, because of the lack of good cell models to follow the nanoscale events involved. ...
Source: PLoS Genetics - October 16, 2023 Category: Genetics & Stem Cells Authors: Adam Wells Source Type: research
Sensing of H < sub > 2 < /sub > O < sub > 2 < /sub > -induced oxidative stress by the UPF factor complex is crucial for activation of < i > catalase-3 < /i > expression in < i > Neurospora < /i >
by Shuangjie Shen, Chengcheng Zhang, Yuanhao Meng, Guofei Cui, Ying Wang, Xiao Liu, Qun He
UPF-1-UPF-2-UPF-3 complex-orchestrated nonsense-mediated mRNA decay (NMD) is a well-characterized eukaryotic cellular surveillance mechanism that not only degrades aberrant transcripts to protect the integrity of the transcriptome but also eliminates normal transcripts to facilitate appropriate cellular responses to physiological and environmental changes. Here, we describe the multifaceted regulatory roles of theNeurospora crassa UPF complex incatalase-3 (cat-3) gene expression, which is essential for scavenging H2O2-induced oxidat...
Source: PLoS Genetics - October 16, 2023 Category: Genetics & Stem Cells Authors: Shuangjie Shen Source Type: research
CAG repeat expansion in the Huntington ’s disease gene shapes linear and circular RNAs biogenesis
by Dilara Ayyildiz, Guendalina Bergonzoni, Alan Monziani, Takshashila Tripathi, Jessica D öring, Emanuela Kerschbamer, Francesca Di Leva, Elia Pennati, Luisa Donini, Marina Kovalenko, Jacopo Zasso, Luciano Conti, Vanessa C. Wheeler, Christoph Dieterich, Silvano Piazza, Erik Dassi, Marta Biagioli
Alternative splicing (AS) appears to be altered in Huntington ’s disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected. Here, taking advantage ofHtt CAG knock-in mousein vitro andin vivo models, we demonstrate a correlation betweenHtt CAG repeat length and increased aberrant linear ...
Source: PLoS Genetics - October 13, 2023 Category: Genetics & Stem Cells Authors: Dilara Ayyildiz Source Type: research
Investigating trait variability of gene co-expression network architecture in brain by controlling for genomic risk of schizophrenia
by Eugenia Radulescu, Qiang Chen, Giulio Pergola, Pasquale Di Carlo, Shizhong Han, Joo Heon Shin, Thomas M. Hyde, Joel E. Kleinman, Daniel R. Weinberger
The effect of schizophrenia (SCZ) genetic risk on gene expression in brain remains elusive. A popular approach to this problem has been the application of gene co-expression network algorithms (e.g., WGCNA). To improve reliability with this method it is critical to remove unwanted sources of variance while also preserving biological signals of interest. In this WCGNA study of RNA-Seq data from postmortem prefrontal cortex (78 neurotypical donors, EUR ancestry), we tested ...
Source: PLoS Genetics - October 13, 2023 Category: Genetics & Stem Cells Authors: Eugenia Radulescu Source Type: research
Revisiting evolutionary trajectories and the organization of the < i > Pleolipoviridae < /i > family
by Tomas Alarc ón-Schumacher, Dominik Lücking, Susanne Erdmann
Archaeal pleomorphic viruses belonging to thePleolipoviridae family represent an enigmatic group as they exhibit unique genomic features and are thought to have evolved through recombination with different archaeal plasmids. However, most of our understanding of the diversity and evolutionary trajectories of this clade comes from a handful of isolated representatives. Here we present 164 new genomes of pleolipoviruses obtained from metagenomic data of Australian hypersaline lakes and publicly available metagenomic data. We perform a comprehensive analysis on...
Source: PLoS Genetics - October 13, 2023 Category: Genetics & Stem Cells Authors: Tomas Alarc ón-Schumacher Source Type: research
Transcriptomic comparison of two selective retinal cell ablation paradigms in zebrafish reveals shared and cell-specific regenerative responses
by Kevin Emmerich, Steven L. Walker, Guohua Wang, David T. White, Anneliese Ceisel, Fang Wang, Yong Teng, Zeeshaan Chunawala, Gianna Graziano, Saumya Nimmagadda, Meera T. Saxena, Jiang Qian, Jeff S. Mumm
Retinal M üller glia (MG) can act as stem-like cells to generate new neurons in both zebrafish and mice. In zebrafish, retinal regeneration is innate and robust, resulting in the replacement of lost neurons and restoration of visual function. In mice, exogenous stimulation of MG is required to reveal a dorma nt and, to date, limited regenerative capacity. Zebrafish studies have been key in revealing factors that promote ...
Source: PLoS Genetics - October 11, 2023 Category: Genetics & Stem Cells Authors: Kevin Emmerich Source Type: research
Unanticipated domain requirements for < i > Drosophila < /i > Wnk kinase < i > in vivo < /i >
by Prathibha Yarikipati, Sima Jonusaite, John M. Pleinis, Carihann Dominicci Cotto, David Sanchez-Hernandez, Daryl E. Morrison, Suhani Goyal, Jeffery Schellinger, Clothilde P énalva, Jennifer Curtiss, Aylin R. Rodan, Andreas Jenny
WNK (With no Lysine [K]) kinases have critical roles in the maintenance of ion homeostasis and the regulation of cell volume. Their overactivation leads to pseudohypoaldosteronism type II (Gordon syndrome) characterized by hyperkalemia and high blood pressure. More recently, WNK family members have been shown to be required for the development of the nervous system in mice, zebrafish, and flies...
Source: PLoS Genetics - October 11, 2023 Category: Genetics & Stem Cells Authors: Prathibha Yarikipati Source Type: research
AGAMOUS mediates timing of guard cell formation during gynoecium development
We present evidence that this regulation by AG is mediated by direct transcriptional repression of a master regulator of the stomatal lineage,MUTE, and show data that suggests this interaction is conserved among several members of the Brassicaceae. This work extends our understanding of the mechanisms underlying floral organ formation and provides a framework to decipher the mechanisms that control floral organ photosynthesis. (Source: PLoS Genetics)
Source: PLoS Genetics - October 11, 2023 Category: Genetics & Stem Cells Authors: Ailbhe J. Brazel Source Type: research
Uptake of environmental DNA in < i > Bacillus subtilis < /i > occurs all over the cell surface through a dynamic pilus structure
by Alexandra Kilb, Marie Burghard-Schrod, Sven Holtrup, Peter L. Graumann
At the transition to stationary phase, a subpopulation ofBacillus subtilis cells can enter the developmental state of competence, where DNA is taken up through the cell envelope, and is processed to single stranded DNA, which is incorporated into the genome if sufficient homology between sequences exists. We show here that the initial step of transport across the cell wall occurs via a true pilus structure, with an average length of about 500 nm, which assembles at various places on the cell surface. Once assembled, the pilus remains at one position...
Source: PLoS Genetics - October 10, 2023 Category: Genetics & Stem Cells Authors: Alexandra Kilb Source Type: research
Insights into the conservation and diversification of the molecular functions of YTHDF proteins
by Daniel Flores-T éllez, Mathias Due Tankmar, Sören von Bülow, Junyu Chen, Kresten Lindorff-Larsen, Peter Brodersen, Laura Arribas-Hernández
YT521-B homology (YTH) domain proteins act as readers ofN6-methyladenosine (m6A) in mRNA. Members of the YTHDF clade determine properties of m6A-containing mRNAs in the cytoplasm. Vertebrates encode three YTHDF proteins whose possible functional specialization is debated. In land plants, the YTHDF clade has expanded from one member in basal lineages to eleven so-called EVOLUTIONARILY CONSERVED C-TERMINAL REGION1-11 (ECT1-11) proteins inArabidopsis thaliana, named after the conse...
Source: PLoS Genetics - October 10, 2023 Category: Genetics & Stem Cells Authors: Daniel Flores-T éllez Source Type: research
Demographically explicit scans for barriers to gene flow using gIMble
by Dominik R. Laetsch, Gertjan Bisschop, Simon H. Martin, Simon Aeschbacher, Derek Setter, Konrad Lohse
Identifying regions of the genome that act as barriers to gene flow between recently diverged taxa has remained challenging given the many evolutionary forces that generate variation in genetic diversity and divergence along the genome, and the stochastic nature of this variation. Progress has been impeded by a conceptual and methodological divide between analyses that infer the demographic history of speciation and genome scans aimed at identifying locally maladaptive alleles i.e. genomic barriers to gene flow. Here we...
Source: PLoS Genetics - October 10, 2023 Category: Genetics & Stem Cells Authors: Dominik R. Laetsch Source Type: research
The selfish yeast plasmid exploits a SWI/SNF-type chromatin remodeling complex for hitchhiking on chromosomes and ensuring high-fidelity propagation
We describe a Rep-STB bypass system in which a plasmid engineered to non-covalently associate with the RSC complex mimics segregation by chromosome hitchhiking. Given the ubiquitous prevalence of SWI/SNF family chromatin remodeling complexes among eukaryotes, it is likely that the 2-micron plasmid paradigm or analogous ones will be encountered among other eukaryotic selfish elements. (Source: PLoS Genetics)
Source: PLoS Genetics - October 9, 2023 Category: Genetics & Stem Cells Authors: Chien-Hui Ma Source Type: research
Constructing and interpreting a large-scale variant effect map for an ultrarare disease gene: Comprehensive prediction of the functional impact of < i > PSAT1 < /i > genotypes
by Michael J. Xie, Gareth A. Cromie, Katherine Owens, Martin S. Timour, Michelle Tang, J. Nathan Kutz, Ayman W. El-Hattab, Richard N. McLaughlin Jr., Aim ée M. Dudley
Reduced activity of the enzymes encoded byPHGDH,PSAT1, andPSPH causes a set of ultrarare, autosomal recessive diseases known as serine biosynthesis defects. These diseases present in a broad phenotypic spectrum: at the severe end is Neu –Laxova syndrome, in the intermediate range are infantile serine biosynthesis defects with severe neurological manifestations and growth deficiency, and at the mild end is childhood disease with intellectual disability. Ho...
Source: PLoS Genetics - October 9, 2023 Category: Genetics & Stem Cells Authors: Michael J. Xie Source Type: research
Identification of a non-canonical ciliate nuclear genetic code where UAA and UAG code for different amino acids
by Jamie McGowan, Estelle S. Kilias, Elisabet Alacid, James Lipscombe, Benjamin H. Jenkins, Karim Gharbi, Gemy G. Kaithakottil, Iain C. Macaulay, Seanna McTaggart, Sally D. Warring, Thomas A. Richards, Neil Hall, David Swarbreck
The genetic code is one of the most highly conserved features across life. Only a few lineages have deviated from the “universal” genetic code. Amongst the few variants of the genetic code reported to date, the codons UAA and UAG virtually always have the same translation, suggesting that their evolution is coupled. Here, we report the genome and transcriptome sequencing of a novel uncultured ...
Source: PLoS Genetics - October 5, 2023 Category: Genetics & Stem Cells Authors: Jamie McGowan Source Type: research
Elevated levels of sphingolipid MIPC in the plasma membrane disrupt the coordination of cell growth with cell wall formation in fission yeast
by Alaina H. Willet, Marcin Wos, Maya G. Igarashi, Liping Ren, Lesley A. Turner, Kathleen L. Gould
Coupling cell wall expansion with cell growth is a universal challenge faced by walled organisms. Mutations inSchizosaccharomyces pombe css1, which encodes a PM inositol phosphosphingolipid phospholipase C, prevent cell wall expansion but not synthesis of cell wall material. To probe how Css1 modulates cell wall formation we used classical and chemical genetics coupled with quantitative mass spectrometry. We found that elevated levels of the sphingolipid biosynthetic pathway ’s final product, mannosylinositol phosphorylcer...
Source: PLoS Genetics - October 4, 2023 Category: Genetics & Stem Cells Authors: Alaina H. Willet Source Type: research
