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Electrical synapse structure requires distinct isoforms of a postsynaptic scaffold. PLOS Genet. (IF 4.5) Pub Date : 2023-11-27 Jennifer Carlisle Michel,Margaret M B Grivette,Amber T Harshfield,Lisa Huynh,Ava P Komons,Bradley Loomis,Kaitlan McKinnis,Brennen T Miller,Ethan Q Nguyen,Tiffany W Huang,Sophia Lauf,Elias S Michel,Mia E Michel,Jane S Kissinger,Audrey J Marsh,William E Crow,Lila E Kaye,Abagael M Lasseigne,Rachel M Lukowicz-Bedford,Dylan R Farnsworth,E Anne Martin,Adam C Miller
Electrical synapses are neuronal gap junction (GJ) channels associated with a macromolecular complex called the electrical synapse density (ESD), which regulates development and dynamically modifies electrical transmission. However, the proteomic makeup and molecular mechanisms utilized by the ESD that direct electrical synapse formation are not well understood. Using the Mauthner cell of zebrafish
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Functional and evolutionary analysis of host Synaptogyrin-2 in porcine circovirus type 2 susceptibility. PLOS Genet. (IF 4.5) Pub Date : 2023-11-27 Lianna R Walker,Hiep L Vu,Kristi L Montooth,Daniel C Ciobanu
Mammalian evolution has been influenced by viruses for millions of years, leaving signatures of adaptive evolution within genes encoding for viral interacting proteins. Synaptogyrin-2 (SYNGR2) is a transmembrane protein implicated in promoting bacterial and viral infections. A genome-wide association study of pigs experimentally infected with porcine circovirus type 2b (PCV2b) uncovered a missense
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ZmEREB92 plays a negative role in seed germination by regulating ethylene signaling and starch mobilization in maize. PLOS Genet. (IF 4.5) Pub Date : 2023-11-17 Jingye Fu,Wenzheng Pei,Linqian He,Ben Ma,Chen Tang,Li Zhu,Liping Wang,Yuanyuan Zhong,Gang Chen,Qi Wang,Qiang Wang
Rapid and uniform seed germination is required for modern cropping system. Thus, it is important to optimize germination performance through breeding strategies in maize, in which identification for key regulators is needed. Here, we characterized an AP2/ERF transcription factor, ZmEREB92, as a negative regulator of seed germination in maize. Enhanced germination in ereb92 mutants is contributed by
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Cross-ancestry analyses identify new genetic loci associated with 25-hydroxyvitamin D. PLOS Genet. (IF 4.5) Pub Date : 2023-11-14 Xiaotong Wang,Valentin Hivert,Shiane Groot,Ying Wang,Loic Yengo,John J McGrath,Kathryn E Kemper,Peter M Visscher,Naomi R Wray,Joana A Revez
Vitamin D status-a complex trait influenced by environmental and genetic factors-is tightly associated with skin colour and ancestry. Yet very few studies have investigated the genetic underpinnings of vitamin D levels across diverse ancestries, and the ones that have, relied on small sample sizes, resulting in inconclusive results. Here, we conduct genome-wide association studies (GWAS) of 25 hydroxyvitamin
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Genome mining yields putative disease-associated ROMK variants with distinct defects. PLOS Genet. (IF 4.5) Pub Date : 2023-11-13 Nga H Nguyen,Srikant Sarangi,Erin M McChesney,Shaohu Sheng,Jacob D Durrant,Aidan W Porter,Thomas R Kleyman,Zachary W Pitluk,Jeffrey L Brodsky
Bartter syndrome is a group of rare genetic disorders that compromise kidney function by impairing electrolyte reabsorption. Left untreated, the resulting hyponatremia, hypokalemia, and dehydration can be fatal, and there is currently no cure. Bartter syndrome type II specifically arises from mutations in KCNJ1, which encodes the renal outer medullary potassium channel, ROMK. Over 40 Bartter syndrome-associated
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MIWI N-terminal RG motif promotes efficient pachytene piRNA production and spermatogenesis independent of LINE1 transposon silencing. PLOS Genet. (IF 4.5) Pub Date : 2023-11-13 Chao Wei,Jiongjie Jing,Xiaoyuan Yan,Jeffrey M Mann,Ruirong Geng,Huirong Xie,Elena Y Demireva,Rex A Hess,Deqiang Ding,Chen Chen
PIWI proteins and their associated piRNAs act to silence transposons and promote gametogenesis. Murine PIWI proteins MIWI, MILI, and MIWI2 have multiple arginine and glycine (RG)-rich motifs at their N-terminal domains. Despite being known as docking sites for the TDRD family proteins, the in vivo regulatory roles for these RG motifs in directing PIWI in piRNA biogenesis and spermatogenesis remain
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Correction: Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions. PLOS Genet. (IF 4.5) Pub Date : 2023-11-13 David Melamed,Aaron Choi,Amy Reilein,Simon Tavaré,Daniel Kalderon
[This corrects the article DOI: 10.1371/journal.pgen.1010965.].
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Context-dependent ciliary regulation of hedgehog pathway repression in tissue morphogenesis. PLOS Genet. (IF 4.5) Pub Date : 2023-11-09 Sun-Hee Hwang,Kevin Andrew White,Bandarigoda Nipunika Somatilaka,Baolin Wang,Saikat Mukhopadhyay
A fundamental problem in tissue morphogenesis is identifying how subcellular signaling regulates mesoscale organization of tissues. The primary cilium is a paradigmatic organelle for compartmentalized subcellular signaling. How signaling emanating from cilia orchestrates tissue organization-especially, the role of cilia-generated effectors in mediating diverse morpho-phenotypic outcomes-is not well
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Lineage-specific genes are clustered with HET-domain genes and respond to environmental and genetic manipulations regulating reproduction in Neurospora. PLOS Genet. (IF 4.5) Pub Date : 2023-11-07 Zheng Wang,Yen-Wen Wang,Takao Kasuga,Francesc Lopez-Giraldez,Yang Zhang,Zhang Zhang,Yaning Wang,Caihong Dong,Anita Sil,Frances Trail,Oded Yarden,Jeffrey P Townsend
Lineage-specific genes (LSGs) have long been postulated to play roles in the establishment of genetic barriers to intercrossing and speciation. In the genome of Neurospora crassa, most of the 670 Neurospora LSGs that are aggregated adjacent to the telomeres are clustered with 61% of the HET-domain genes, some of which regulate self-recognition and define vegetative incompatibility groups. In contrast
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Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling. PLOS Genet. (IF 4.5) Pub Date : 2023-11-07 Ronit Marom,Bo Zhang,Megan E Washington,I-Wen Song,Lindsay C Burrage,Vittoria C Rossi,Ava S Berrier,Anika Lindsey,Jacob Lesinski,Michael L Nonet,Jian Chen,Dustin Baldridge,Gary A Silverman,V Reid Sutton,Jill A Rosenfeld,Alyssa A Tran,M John Hicks,David R Murdock,Hongzheng Dai,MaryAnn Weis,Shalini N Jhangiani,Donna M Muzny,Richard A Gibbs,Richard Caswell,Carrie Pottinger,Deirdre Cilliers,Karen Stals
BACKGROUND Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly
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PGP-14 establishes a polar lipid permeability barrier within the C. elegans pharyngeal cuticle. PLOS Genet. (IF 4.5) Pub Date : 2023-11-06 Muntasir Kamal,Levon Tokmakjian,Jessica Knox,Duhyun Han,Houtan Moshiri,Lilia Magomedova,Ken Cq Nguyen,Hong Zheng,Andrew R Burns,Brittany Cooke,Jessica Lacoste,May Yeo,David H Hall,Carolyn L Cummins,Peter J Roy
The cuticles of ecdysozoan animals are barriers to material loss and xenobiotic insult. Key to this barrier is lipid content, the establishment of which is poorly understood. Here, we show that the p-glycoprotein PGP-14 functions coincidently with the sphingomyelin synthase SMS-5 to establish a polar lipid barrier within the pharyngeal cuticle of the nematode C. elegans. We show that PGP-14 and SMS-5
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Deletions of singular U1 snRNA gene significantly interfere with transcription and 3'-end mRNA formation. PLOS Genet. (IF 4.5) Pub Date : 2023-11-02 Mei Wang,An-Min Liang,Zhen-Zhen Zhou,Ting-Lin Pang,Yu-Jie Fan,Yong-Zhen Xu
Small nuclear RNAs (snRNAs) are structural and functional cores of the spliceosome. In metazoan genomes, each snRNA has multiple copies/variants, up to hundreds in mammals. However, the expressions and functions of each copy/variant in one organism have not been systematically studied. Focus on U1 snRNA genes, we investigated all five copies in Drosophila melanogaster using two series of constructed
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Genome-wide census of ATF4 binding sites and functional profiling of trait-associated genetic variants overlapping ATF4 binding motifs. PLOS Genet. (IF 4.5) Pub Date : 2023-10-31 Tiit Örd,Daima Örd,Priit Adler,Tõnis Örd
Activating Transcription Factor 4 (ATF4) is an important regulator of gene expression in stress responses and developmental processes in many cell types. Here, we catalogued ATF4 binding sites in the human genome and identified overlaps with trait-associated genetic variants. We probed these genetic variants for allelic regulatory activity using a massively parallel reporter assay (MPRA) in HepG2 hepatoma
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Meta-analysis of genome-wide association studies of gestational duration and spontaneous preterm birth identifies new maternal risk loci. PLOS Genet. (IF 4.5) Pub Date : 2023-10-23 Anu Pasanen,Minna K Karjalainen,,Ge Zhang,Heli Tiensuu,Antti M Haapalainen,Marja Ojaniemi,Bjarke Feenstra,Bo Jacobsson,Aarno Palotie,Hannele Laivuori,Louis J Muglia,Mika Rämet,Mikko Hallman
BACKGROUND Preterm birth (<37 weeks of gestation) is a major cause of neonatal death and morbidity. Up to 40% of the variation in timing of birth results from genetic factors, mostly due to the maternal genome. METHODS We conducted a genome-wide meta-analysis of gestational duration and spontaneous preterm birth in 68,732 and 98,370 European mothers, respectively. RESULTS The meta-analysis detected
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A novel proneural function of Asense is integrated with the sequential actions of Delta-Notch, L'sc and Su(H) to promote the neuroepithelial to neuroblast transition. PLOS Genet. (IF 4.5) Pub Date : 2023-10-23 Mercedes Martin,Francisco Gutierrez-Avino,Mirja N Shaikh,Francisco J Tejedor
In order for neural progenitors (NPs) to generate distinct populations of neurons at the right time and place during CNS development, they must switch from undergoing purely proliferative, self-renewing divisions to neurogenic, asymmetric divisions in a tightly regulated manner. In the developing Drosophila optic lobe, neuroepithelial (NE) cells of the outer proliferation center (OPC) are progressively
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The parenting hub of the hypothalamus is a focus of imprinted gene action. PLOS Genet. (IF 4.5) Pub Date : 2023-10-19 Matthew J Higgs,Anna E Webberley,Alasdair J Allan,Moaz Talat,Rosalind M John,Anthony R Isles
Imprinted genes are subject to germline epigenetic modification resulting in parental-specific allelic silencing. Although genomic imprinting is thought to be important for maternal behaviour, this idea is based on serendipitous findings from a small number of imprinted genes. Here, we undertook an unbiased systems biology approach, taking advantage of the recent delineation of specific neuronal populations
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lhCLIP reveals the in vivo RNA-RNA interactions recognized by hnRNPK. PLOS Genet. (IF 4.5) Pub Date : 2023-10-18 Yuanlang Hu,Tao Hao,Hanwen Yu,Wenbin Miao,Yi Zheng,Weihua Tao,Jingshen Zhuang,Jichang Wang,Yujuan Fan,Shiqi Jia
RNA-RNA interactions play a crucial role in regulating gene expression and various biological processes, but identifying these interactions on a transcriptomic scale remains a challenge. To address this, we have developed a new biochemical technique called pCp-biotin labelled RNA hybrid and ultraviolet crosslinking and immunoprecipitation (lhCLIP) that enables the transcriptome-wide identification
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Genome wide association joint analysis reveals 99 risk loci for pain susceptibility and pleiotropic relationships with psychiatric, metabolic, and immunological traits. PLOS Genet. (IF 4.5) Pub Date : 2023-10-16 Evelina Mocci,Kathryn Ward,James A Perry,Angela Starkweather,Laura S Stone,Siobhan M Schabrun,Cynthia Renn,Susan G Dorsey,Seth A Ament
Chronic pain is at epidemic proportions in the United States, represents a significant burden on our public health system, and is coincident with a growing opioid crisis. While numerous genome-wide association studies have been reported for specific pain-related traits, many of these studies were underpowered, and the genetic relationship among these traits remains poorly understood. Here, we conducted
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Sensing of H2O2-induced oxidative stress by the UPF factor complex is crucial for activation of catalase-3 expression in Neurospora. PLOS Genet. (IF 4.5) Pub Date : 2023-10-16 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
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CAG repeat expansion in the Huntington's disease gene shapes linear and circular RNAs biogenesis. PLOS Genet. (IF 4.5) Pub Date : 2023-10-13 Dilara Ayyildiz,Guendalina Bergonzoni,Alan Monziani,Takshashila Tripathi,Jessica Döring,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 of Htt CAG knock-in mouse in vitro and in vivo models, we demonstrate a correlation between Htt CAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and, in vivo, the striatum
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Investigating trait variability of gene co-expression network architecture in brain by controlling for genomic risk of schizophrenia. PLOS Genet. (IF 4.5) Pub Date : 2023-10-13 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
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Revisiting evolutionary trajectories and the organization of the Pleolipoviridae family. PLOS Genet. (IF 4.5) Pub Date : 2023-10-13 Tomas Alarcón-Schumacher,Dominik Lücking,Susanne Erdmann
Archaeal pleomorphic viruses belonging to the Pleolipoviridae 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
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Unanticipated domain requirements for Drosophila Wnk kinase in vivo. PLOS Genet. (IF 4.5) Pub Date : 2023-10-11 Prathibha Yarikipati,Sima Jonusaite,John M Pleinis,Carihann Dominicci Cotto,David Sanchez-Hernandez,Daryl E Morrison,Suhani Goyal,Jeffrey Schellinger,Clothilde Pénalva,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, and
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Constructing and interpreting a large-scale variant effect map for an ultrarare disease gene: Comprehensive prediction of the functional impact of PSAT1 genotypes. PLOS Genet. (IF 4.5) Pub Date : 2023-10-09 Michael J Xie,Gareth A Cromie,Katherine Owens,Martin S Timour,Michelle Tang,J Nathan Kutz,Ayman W El-Hattab,Richard N McLaughlin,Aimée M Dudley
Reduced activity of the enzymes encoded by PHGDH, PSAT1, and PSPH 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
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O antigen biogenesis sensitises Escherichia coli K-12 to bile salts, providing a plausible explanation for its evolutionary loss. PLOS Genet. (IF 4.5) Pub Date : 2023-10-04 Jilong Qin,Yaoqin Hong,Renato Morona,Makrina Totsika
Escherichia coli K-12 is a model organism for bacteriology and has served as a workhorse for molecular biology and biochemistry for over a century since its first isolation in 1922. However, Escherichia coli K-12 strains are phenotypically devoid of an O antigen (OAg) since early reports in the scientific literature. Recent studies have reported the presence of independent mutations that abolish OAg
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Elevated levels of sphingolipid MIPC in the plasma membrane disrupt the coordination of cell growth with cell wall formation in fission yeast. PLOS Genet. (IF 4.5) Pub Date : 2023-10-04 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 in Schizosaccharomyces 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
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Functional dissection and assembly of a small, newly evolved, W chromosome-specific genomic region of the African clawed frog Xenopus laevis. PLOS Genet. (IF 4.5) Pub Date : 2023-10-04 Caroline M S Cauret,Danielle C Jordan,Lindsey M Kukoly,Sarah R Burton,Emmanuela U Anele,Jacek M Kwiecien,Marie-Theres Gansauge,Sinthu Senthillmohan,Eli Greenbaum,Matthias Meyer,Marko E Horb,Ben J Evans
Genetic triggers for sex determination are frequently co-inherited with other linked genes that may also influence one or more sex-specific phenotypes. To better understand how sex-limited regions evolve and function, we studied a small W chromosome-specific region of the frog Xenopus laevis that contains only three genes (dm-w, scan-w, ccdc69-w) and that drives female differentiation. Using gene editing
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Neurodevelopmental deficits and cell-type-specific transcriptomic perturbations in a mouse model of HNRNPU haploinsufficiency. PLOS Genet. (IF 4.5) Pub Date : 2023-10-02 Sarah A Dugger,Ryan S Dhindsa,Gabriela De Almeida Sampaio,Andrew K Ressler,Elizabeth E Rafikian,Sabrina Petri,Verity A Letts,JiaJie Teoh,Junqiang Ye,Sophie Colombo,Yueqing Peng,Mu Yang,Michael J Boland,Wayne N Frankel,David B Goldstein
Heterozygous de novo loss-of-function mutations in the gene expression regulator HNRNPU cause an early-onset developmental and epileptic encephalopathy. To gain insight into pathological mechanisms and lay the potential groundwork for developing targeted therapies, we characterized the neurophysiologic and cell-type-specific transcriptomic consequences of a mouse model of HNRNPU haploinsufficiency
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Genome-wide single-molecule analysis of long-read DNA methylation reveals heterogeneous patterns at heterochromatin that reflect nucleosome organisation. PLOS Genet. (IF 4.5) Pub Date : 2023-10-02 Lyndsay Kerr,Ioannis Kafetzopoulos,Ramon Grima,Duncan Sproul
High-throughput sequencing technology is central to our current understanding of the human methylome. The vast majority of studies use chemical conversion to analyse bulk-level patterns of DNA methylation across the genome from a population of cells. While this technology has been used to probe single-molecule methylation patterns, such analyses are limited to short reads of a few hundred basepairs
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Adenylosuccinate lyase deficiency affects neurobehavior via perturbations to tyramine signaling in Caenorhabditis elegans. PLOS Genet. (IF 4.5) Pub Date : 2023-09-29 Corinna A Moro,Sabrina A Sony,Latisha P Franklin,Shirley Dong,Mia M Peifer,Kathryn E Wittig,Wendy Hanna-Rose
Adenylosuccinate lyase deficiency is an ultrarare congenital metabolic disorder associated with muscle weakness and neurobehavioral dysfunction. Adenylosuccinate lyase is required for de novo purine biosynthesis, acting twice in the pathway at non-sequential steps. Genetic models can contribute to our understanding of the etiology of disease phenotypes and pave the way for development of therapeutic
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A double-negative feedback loop between miR319c and JAW-TCPs establishes growth pattern in incipient leaf primordia in Arabidopsis thaliana. PLOS Genet. (IF 4.5) Pub Date : 2023-09-28 Naveen Shankar,Preethi Sunkara,Utpal Nath
The microRNA miR319 and its target JAW-TCP transcription factors regulate the proliferation-to-differentiation transition of leaf pavement cells in diverse plant species. In young Arabidopsis leaf primordia, JAW-TCPs are detected towards the distal region whereas the major mRNA319-encoding gene MIR319C, is expressed at the base. Little is known about how this complementary expression pattern of MIR319C
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RBMX involves in telomere stability maintenance by regulating TERRA expression. PLOS Genet. (IF 4.5) Pub Date : 2023-09-27 Jingfan Liu,Tian Zheng,Dandan Chen,Junjiu Huang,Yong Zhao,Wenbin Ma,Haiying Liu
Telomeric repeat-containing RNA (TERRA) is a class of long noncoding RNAs (lncRNAs) that are transcribed from subtelomeric to telomeric region of chromosome ends. TERRA is prone to form R-loop structures at telomeres by invading into telomeric DNA. Excessive telomere R-loops result in telomere instability, so the TERRA level needs to be delicately modulated. However, the molecular mechanisms and factors
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A digital twin reproducing gene regulatory network dynamics of early Ciona embryos indicates robust buffers in the network. PLOS Genet. (IF 4.5) Pub Date : 2023-09-27 Miki Tokuoka,Yutaka Satou
How gene regulatory networks (GRNs) encode gene expression dynamics and how GRNs evolve are not well understood, although these problems have been studied extensively. We created a digital twin that accurately reproduces expression dynamics of 13 genes that initiate expression in 32-cell ascidian embryos. We first showed that gene expression patterns can be manipulated according to predictions by this
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Notch pathway mutants do not equivalently perturb mouse embryonic retinal development. PLOS Genet. (IF 4.5) Pub Date : 2023-09-26 Bernadett Bosze,Julissa Suarez-Navarro,Illiana Cajias,Joseph A Brzezinski Iv,Nadean L Brown
In the vertebrate eye, Notch ligands, receptors, and ternary complex components determine the destiny of retinal progenitor cells in part by regulating Hes effector gene activity. There are multiple paralogues for nearly every node in this pathway, which results in numerous instances of redundancy and compensation during development. To dissect such complexity at the earliest stages of eye development
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Chromatin accessibility, not 5mC methylation covaries with partial dosage compensation in crows. PLOS Genet. (IF 4.5) Pub Date : 2023-09-25 Ana Catalán,Justin Merondun,Ulrich Knief,Jochen B W Wolf
The evolution of genetic sex determination is often accompanied by degradation of the sex-limited chromosome. Male heterogametic systems have evolved convergent, epigenetic mechanisms restoring the resulting imbalance in gene dosage between diploid autosomes (AA) and the hemizygous sex chromosome (X). Female heterogametic systems (AAf Zf, AAm ZZm) tend to only show partial dosage compensation (0.5
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H4K20me3 is important for Ash1-mediated H3K36me3 and transcriptional silencing in facultative heterochromatin in a fungal pathogen. PLOS Genet. (IF 4.5) Pub Date : 2023-09-25 Mareike Möller,John B Ridenour,Devin F Wright,Faith A Martin,Michael Freitag
Facultative heterochromatin controls development and differentiation in many eukaryotes. In metazoans, plants, and many filamentous fungi, facultative heterochromatin is characterized by transcriptional repression and enrichment with nucleosomes that are trimethylated at histone H3 lysine 27 (H3K27me3). While loss of H3K27me3 results in derepression of transcriptional gene silencing in many species
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Abnormal outer hair cell efferent innervation in Hoxb1-dependent sensorineural hearing loss. PLOS Genet. (IF 4.5) Pub Date : 2023-09-22 Maria Di Bonito,Jérôme Bourien,Monica Tizzano,Anne-Gabrielle Harrus,Jean-Luc Puel,Bice Avallone,Regis Nouvian,Michèle Studer
Autosomal recessive mutation of HOXB1 and Hoxb1 causes sensorineural hearing loss in patients and mice, respectively, characterized by the presence of higher auditory thresholds; however, the origin of the defects along the auditory pathway is still unknown. In this study, we assessed whether the abnormal auditory threshold and malformation of the sensory auditory cells, the outer hair cells, described
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Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer. PLOS Genet. (IF 4.5) Pub Date : 2023-09-22 Jingxiong Xu,Wei Xu,Jiyeon Choi,Yonathan Brhane,David C Christiani,Jui Kothari,James McKay,John K Field,Michael P A Davies,Geoffrey Liu,Christopher I Amos,Rayjean J Hung,Laurent Briollais
Common genetic variants associated with lung cancer have been well studied in the past decade. However, only 12.3% heritability has been explained by these variants. In this study, we investigate the contribution of rare variants (RVs) (minor allele frequency <0.01) to lung cancer through two large whole exome sequencing case-control studies. We first performed gene-based association tests using a
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Neuronal expression in Drosophila of an evolutionarily conserved metallophosphodiesterase reveals pleiotropic roles in longevity and odorant response. PLOS Genet. (IF 4.5) Pub Date : 2023-09-21 Kriti Gupta,Sveta Chakrabarti,Vishnu Janardan,Nishita Gogia,Sanghita Banerjee,Swarna Srinivas,Deepthi Mahishi,Sandhya S Visweswariah
Evolutionarily conserved genes often play critical roles in organismal physiology. Here, we describe multiple roles of a previously uncharacterized Class III metallophosphodiesterase in Drosophila, an ortholog of the MPPED1 and MPPED2 proteins expressed in the mammalian brain. dMpped, the product of CG16717, hydrolyzed phosphodiester substrates including cAMP and cGMP in a metal-dependent manner. dMpped
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Methionine biosynthesis enzyme MoMet2 is required for rice blast fungus pathogenicity by promoting virulence gene expression via reducing 5mC modification. PLOS Genet. (IF 4.5) Pub Date : 2023-09-21 Huimin Li,Pengcheng Mo,Jun Zhang,Zhuoer Xie,Xinyu Liu,Han Chen,Leiyun Yang,Muxing Liu,Haifeng Zhang,Ping Wang,Zhengguang Zhang
The emergence of fungicide resistance severely threatens crop production by limiting the availability and application of established fungicides. Therefore, it is urgent to identify new fungicidal targets for controlling plant diseases. Here, we characterized the function of a conserved homoserine O-acetyltransferase (HOA) from the rice blast fungus Magnaporthe oryzae that could serve as the candidate
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Non-gonadal somatic piRNA pathways ensure sexual differentiation, larval growth, and wing development in silkworms. PLOS Genet. (IF 4.5) Pub Date : 2023-09-21 Takashi Kiuchi,Keisuke Shoji,Natsuko Izumi,Yukihide Tomari,Susumu Katsuma
PIWI-interacting RNAs (piRNAs) guide PIWI proteins to target transposons in germline cells, thereby suppressing transposon activity to preserve genome integrity in metazoans' gonadal tissues. Piwi, one of three Drosophila PIWI proteins, is expressed in the nucleus and suppresses transposon activity by forming heterochromatin in an RNA cleavage-independent manner. Recently, Piwi was reported to control
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MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity. PLOS Genet. (IF 4.5) Pub Date : 2023-09-20 Jianxin Xie,Wei Zou,Madina Tugizova,Kang Shen,Xiangming Wang
Transcription factors (TFs) play critical roles in specifying many aspects of neuronal cell fate including dendritic morphology. How TFs are accurately regulated during neuronal morphogenesis is not fully understood. Here, we show that LIM homeodomain protein MEC-3, the key TF for C. elegans PVD dendrite morphogenesis, is regulated by both alternative splicing and an E3 ubiquitin ligase. The mec-3
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Structural transitions upon guide RNA binding and their importance in Cas12g-mediated RNA cleavage. PLOS Genet. (IF 4.5) Pub Date : 2023-09-20 Mengxi Liu,Zekai Li,Jing Chen,Jinying Lin,Qiuhua Lu,Yangmiao Ye,Hongmin Zhang,Bo Zhang,Songying Ouyang
Cas12g is an endonuclease belonging to the type V RNA-guided CRISPR-Cas family. It is known for its ability to cleave RNA substrates using a conserved endonuclease active site located in the RuvC domain. In this study, we determined the crystal structure of apo-Cas12g, the cryo-EM structure of the Cas12g-sgRNA binary complex and investigated conformational changes that occur during the transition from
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eQTL Catalogue 2023: New datasets, X chromosome QTLs, and improved detection and visualisation of transcript-level QTLs. PLOS Genet. (IF 4.5) Pub Date : 2023-09-18 Nurlan Kerimov,Ralf Tambets,James D Hayhurst,Ida Rahu,Peep Kolberg,Uku Raudvere,Ivan Kuzmin,Anshika Chowdhary,Andreas Vija,Hans J Teras,Masahiro Kanai,Jacob Ulirsch,Mina Ryten,John Hardy,Sebastian Guelfi,Daniah Trabzuni,Sarah Kim-Hellmuth,William Rayner,Hilary Finucane,Hedi Peterson,Abayomi Mosaku,Helen Parkinson,Kaur Alasoo
The eQTL Catalogue is an open database of uniformly processed human molecular quantitative trait loci (QTLs). We are continuously updating the resource to further increase its utility for interpreting genetic associations with complex traits. Over the past two years, we have increased the number of uniformly processed studies from 21 to 31 and added X chromosome QTLs for 19 compatible studies. We have
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Saturation genome editing of 11 codons and exon 13 of BRCA2 coupled with chemotherapeutic drug response accurately determines pathogenicity of variants. PLOS Genet. (IF 4.5) Pub Date : 2023-09-15 Sounak Sahu,Teresa L Sullivan,Alexander Y Mitrophanov,Mélissa Galloux,Darryl Nousome,Eileen Southon,Dylan Caylor,Arun Prakash Mishra,Christine N Evans,Michelle E Clapp,Sandra Burkett,Tyler Malys,Raj Chari,Kajal Biswas,Shyam K Sharan
The unknown pathogenicity of a significant number of variants found in cancer-related genes is attributed to limited epidemiological data, resulting in their classification as variant of uncertain significance (VUS). To date, Breast Cancer gene-2 (BRCA2) has the highest number of VUSs, which has necessitated the development of several robust functional assays to determine their functional significance
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Rescue of bmp15 deficiency in zebrafish by mutation of inha reveals mechanisms of BMP15 regulation of folliculogenesis. PLOS Genet. (IF 4.5) Pub Date : 2023-09-15 Yue Zhai,Xin Zhang,Cheng Zhao,Ruijing Geng,Kun Wu,Mingzhe Yuan,Nana Ai,Wei Ge
As an oocyte-specific growth factor, bone morphogenetic protein 15 (BMP15) plays a critical role in controlling folliculogenesis. However, the mechanism of BMP15 action remains elusive. Using zebrafish as the model, we created a bmp15 mutant using CRISPR/Cas9 and demonstrated that bmp15 deficiency caused a significant delay in follicle activation and puberty onset followed by a complete arrest of follicle
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A detoxification pathway initiated by a nuclear receptor TcHR96h in Tetranychus cinnabarinus (Boisduval). PLOS Genet. (IF 4.5) Pub Date : 2023-09-14 Xiang Wen,Kaiyang Feng,Juan Qin,Peng Wei,Peng Cao,Youjun Zhang,Zhiguang Yuchi,Lin He
Understanding the mechanism of detoxification initiation in arthropods after pesticide exposure is crucial. Although the identity of transcription factors that induce and regulate the expression of detoxification genes in response to pesticides is beginning to emerge, whether transcription factors directly interact with xenobiotics is unclear. The findings of this study revealed that a nuclear hormone
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Histone methylation regulates reproductive diapause in Drosophila melanogaster. PLOS Genet. (IF 4.5) Pub Date : 2023-09-13 Abigail DiVito Evans,Regina A Fairbanks,Paul Schmidt,Mia T Levine
Fluctuating environments threaten fertility and viability. To better match the immediate, local environment, many organisms adopt alternative phenotypic states, a phenomenon called "phenotypic plasticity." Natural populations that predictably encounter fluctuating environments tend to be more plastic than conspecific populations that encounter a constant environment, suggesting that phenotypic plasticity
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Inferring gene regulatory network from single-cell transcriptomes with graph autoencoder model. PLOS Genet. (IF 4.5) Pub Date : 2023-09-13 Jiacheng Wang,Yaojia Chen,Quan Zou
The gene regulatory structure of cells involves not only the regulatory relationship between two genes, but also the cooperative associations of multiple genes. However, most gene regulatory network inference methods for single cell only focus on and infer the regulatory relationships of pairs of genes, ignoring the global regulatory structure which is crucial to identify the regulations in the complex
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Steroid receptor coactivator TAIMAN is a new modulator of insect circadian clock. PLOS Genet. (IF 4.5) Pub Date : 2023-09-08 Vlastimil Smykal,Lenka Chodakova,Marketa Hejnikova,Kristina Briedikova,Bulah Chia-Hsiang Wu,Hana Vaneckova,Ping Chen,Anna Janovska,Pavlina Kyjakova,Martin Vacha,David Dolezel
TAIMAN (TAI), the only insect ortholog of mammalian Steroid Receptor Coactivators (SRCs), is a critical modulator of ecdysone and juvenile hormone (JH) signaling pathways, which govern insect development and reproduction. The modulatory effect is mediated by JH-dependent TAI's heterodimerization with JH receptor Methoprene-tolerant and association with the Ecdysone Receptor complex. Insect hormones
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Evolutionary conserved circular MEF2A RNAs regulate myogenic differentiation and skeletal muscle development. PLOS Genet. (IF 4.5) Pub Date : 2023-09-07 Xiaoxu Shen,Xiyu Zhao,Haorong He,Jing Zhao,Yuanhang Wei,Yuqi Chen,Shunshun Han,Yifeng Zhu,Yao Zhang,Qing Zhu,Huadong Yin
Circular RNAs (circRNAs) have been recognized as critical regulators of skeletal muscle development. Myocyte enhancer factor 2A (MEF2A) is an evolutionarily conserved transcriptional factor that regulates myogenesis. However, it remains unclear whether MEF2A produces functional circRNAs. In this study, we identified two evolutionarily conserved circular MEF2A RNAs (circMEF2As), namely circMEF2A1 and
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Modeling of African population history using f-statistics is biased when applying all previously proposed SNP ascertainment schemes. PLOS Genet. (IF 4.5) Pub Date : 2023-09-07 Pavel Flegontov,Ulaş Işıldak,Robert Maier,Eren Yüncü,Piya Changmai,David Reich
f-statistics have emerged as a first line of analysis for making inferences about demographic history from genome-wide data. Not only are they guaranteed to allow robust tests of the fits of proposed models of population history to data when analyzing full genome sequencing data-that is, all single nucleotide polymorphisms (SNPs) in the individuals being analyzed-but they are also guaranteed to allow
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Genome-wide fitness profiling reveals molecular mechanisms that bacteria use to interact with Trichoderma atroviride exometabolites. PLOS Genet. (IF 4.5) Pub Date : 2023-08-31 José Manuel Villalobos-Escobedo,Maria Belen Mercado-Esquivias,Catharine Adams,W Berkeley Kauffman,Rex R Malmstrom,Adam M Deutschbauer,N Louise Glass
Trichoderma spp. are ubiquitous rhizosphere fungi capable of producing several classes of secondary metabolites that can modify the dynamics of the plant-associated microbiome. However, the bacterial-fungal mechanisms that mediate these interactions have not been fully characterized. Here, a random barcode transposon-site sequencing (RB-TnSeq) approach was employed to identify bacterial genes important
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Rapid evolutionary diversification of the flamenco locus across simulans clade Drosophila species. PLOS Genet. (IF 4.5) Pub Date : 2023-08-29 Sarah Signor,Jeffrey Vedanayagam,Bernard Y Kim,Filip Wierzbicki,Robert Kofler,Eric C Lai
Suppression of transposable elements (TEs) is paramount to maintain genomic integrity and organismal fitness. In D. melanogaster, the flamenco locus is a master suppressor of TEs, preventing the mobilization of certain endogenous retrovirus-like TEs from somatic ovarian support cells to the germline. It is transcribed by Pol II as a long (100s of kb), single-stranded, primary transcript, and metabolized
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β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development. PLOS Genet. (IF 4.5) Pub Date : 2023-08-28 Michael Ebeid,Ippei Kishimoto,Pooja Roy,Mohd Ali Abbas Zaidi,Alan G Cheng,Sung-Ho Huh
The mammalian cochlea is composed of sensory hair cells as well as multiple different types of non-sensory supporting cells. Pillar cells are one type of supporting cell that form the tunnel of Corti and include two morphologically and functionally distinct subtypes: inner pillar cells (IPCs) and outer pillar cells (OPCs). The processes of specification and differentiation of inner versus outer pillar
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Genetic enhancers of partial PLK1 inhibition reveal hypersensitivity to kinetochore perturbations. PLOS Genet. (IF 4.5) Pub Date : 2023-08-28 Karine Normandin,Jasmin Coulombe-Huntington,Corinne St-Denis,Alexandre Bernard,Mohammed Bourouh,Thierry Bertomeu,Mike Tyers,Vincent Archambault
Polo-like kinase 1 (PLK1) is a serine/threonine kinase required for mitosis and cytokinesis. As cancer cells are often hypersensitive to partial PLK1 inactivation, chemical inhibitors of PLK1 have been developed and tested in clinical trials. However, these small molecule inhibitors alone are not completely effective. PLK1 promotes numerous molecular and cellular events in the cell division cycle and
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Localization of oskar mRNA by agglomeration in ribonucleoprotein granules. PLOS Genet. (IF 4.5) Pub Date : 2023-08-25 Catherine E Eichler,Hui Li,Michelle E Grunberg,Elizabeth R Gavis
Localization of oskar mRNA to the posterior of the Drosophila oocyte is essential for abdominal patterning and germline development. oskar localization is a multi-step process involving temporally and mechanistically distinct transport modes. Numerous cis-acting elements and trans-acting factors have been identified that mediate earlier motor-dependent transport steps leading to an initial accumulation
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Artificial selection reveals complex genetic architecture of shoot branching and its response to nitrate supply in Arabidopsis. PLOS Genet. (IF 4.5) Pub Date : 2023-08-24 Hugo Tavares,Anne Readshaw,Urszula Kania,Maaike de Jong,Raj K Pasam,Hayley McCulloch,Sally Ward,Liron Shenhav,Elizabeth Forsyth,Ottoline Leyser
Quantitative traits may be controlled by many loci, many alleles at each locus, and subject to genotype-by-environment interactions, making them difficult to map. One example of such a complex trait is shoot branching in the model plant Arabidopsis, and its plasticity in response to nitrate. Here, we use artificial selection under contrasting nitrate supplies to dissect the genetic architecture of