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The last 50 bibliographies

Males as somatic investment in a parthenogenetic nematode.

Author(s) : Grosmaire M, Launay C, Siegwald M, Brugiere T, Estrada-Virrueta L, Berger D, Burny C, Modolo L, Blaxter M, Meister P, Felix M, Gouyon P, Delattre M,
Journal : Science
2019
We report the reproductive strategy of the nematode Mesorhabditis belari This species produces only 9% males, whose sperm is necessary to fertilize and activate the eggs. However, most of the fertilized eggs develop without using the sperm DNA and produce female individuals. Only in 9% of eggs is the male DNA utilized, producing sons. We found that mixing of parental genomes only gives rise to males because the Y-bearing sperm of males are much more competent than the X-bearing sperm for penetrating the eggs. In this previously unrecognized strategy, asexual females produce few sexual males whose genes never reenter thefemale pool. Here, production of males is of interest only if sons are more likely to mate with their sisters. Using game theory, we show that in this context, the production of 9% males by M. belari females is an evolutionary stable strategy.

The extruded non-template strand determines the architecture of R-loops.

Author(s) : Carrasco-Salas Y, Malapert A, Sulthana S, Molcrette B, Chazot-Franguiadakis L, Bernard P, Chedin F, Faivre-Moskalenko C, Vanoosthuyse V,
Journal : Nucleic Acids Res
2019
Three-stranded R-loop structures have been associated with genomic instability phenotypes. What underlies their wide-ranging effects on genome stability remains poorly understood. Here we combined biochemical and atomic force microscopy approaches with single molecule R-loop footprinting to demonstrate that R-loops formed at the model Airn locus in vitro adopt a defined set of three-dimensionalconformations characterized by distinct shapes and volumes, which we call R-loopobjects. Interestingly, we show that these R-loop objects impose specific physical constraints on the DNA, as revealed by the presence of stereotypical angles in the surrounding DNA. Biochemical probing and mutagenesis experiments revealed that the formation of R-loop objects at Airn is dictated by the extruded non-template strand, suggesting that R-loops possess intrinsic sequence-driven properties. Consistent with this, we show that R-loops formed at the fission yeast gene sum3 do not form detectable R-loop objects. Our results reveal that R-loops differ by their architectures and that the organization of the non-template strand is a fundamental characteristic of R-loops, which could explain that only a subset of R-loops is associated with replication-dependent DNA breaks.

Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9-sgRNA ribonucleoproteins.

Author(s) : Mangeot P, Risson V, Fusil F, Marnef A, Laurent E, Blin J, Mournetas V, Massourides E, Sohier T, Corbin A, Aube F, Teixeira M, Pinset C, Schaeffer L, Legube G, Cosset F, Verhoeyen E, Ohlmann T, Ricci E,
Journal : Nat Commun
2019
Programmable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells and living organisms. However, their delivery into target cellscan be technically challenging when working with primary cells or in vivo. Here,we use engineered murine leukemia virus-like particles loaded with Cas9-sgRNA ribonucleoproteins (Nanoblades) to induce efficient genome-editing in cell linesand primary cells including human induced pluripotent stem cells, human hematopoietic stem cells and mouse bone-marrow cells. Transgene-free Nanoblades are also capable of in vivo genome-editing in mouse embryos and in the liver of injected mice. Nanoblades can be complexed with donor DNA for "all-in-one" homology-directed repair or programmed with modified Cas9 variants to mediate transcriptional up-regulation of target genes. Nanoblades preparation process issimple, relatively inexpensive and can be easily implemented in any laboratory equipped for cellular biology.

System-wide Profiling of RNA-Binding Proteins Uncovers Key Regulators of Virus Infection.

Author(s) : Garcia-Moreno M, Noerenberg M, Ni S, Jarvelin A, Gonzalez-Almela E, Lenz C, Bach-Pages M, Cox V, Avolio R, Davis T, Hester S, Sohier T, Li B, Heikel G, Michlewski G, Sanz M, Carrasco L, Ricci E, Pelechano V, Davis I, Fischer B, Mohammed S, Castello A,
Journal : Mol Cell
2019
The compendium of RNA-binding proteins (RBPs) has been greatly expanded by the development of RNA-interactome capture (RIC). However, it remained unknown if the complement of RBPs changes in response to environmental perturbations and whether these rearrangements are important. To answer these questions, we developed "comparative RIC" and applied it to cells challenged with an RNA virus called sindbis (SINV). Over 200 RBPs display differential interaction with RNA upon SINV infection. These alterations are mainly driven by the loss of cellular mRNAs andthe emergence of viral RNA. RBPs stimulated by the infection redistribute to viral replication factories and regulate the capacity of the virus to infect. For example, ablation of XRN1 causes cells to be refractory to SINV, while GEMIN5 moonlights as a regulator of SINV gene expression. In summary, RNA availability controls RBP localization and function in SINV-infected cells.

Modeling Edar expression reveals the hidden dynamics of tooth signaling center patterning

Author(s) : Sadier A, Twarogowska M, Steklíková k, Hayden L, Lambert A, Schneider P, Laudet V, Hovorakova M, Calvez V, Pantalacci S,
Journal : PLOS Biology
2019

Developmental and comparative transcriptomic identification of iridophore contribution to white barring in clownfish.

Author(s) : Salis P, Lorin T, Lewis V, Rey C, Marcionetti A, Escande M, Roux N, Besseau L, Salamin N, Semon M, Parichy D, Volff J, Laudet V,
Journal : Pigment Cell Melanoma Res
2019
Actinopterygian fishes harbor at least eight distinct pigment cell types, leading to a fascinating diversity of colors. Among this diversity, the cellular origin of the white color appears to be linked to several pigment cell types such as iridophores or leucophores. We used the clownfish Amphiprion ocellaris, which has a color pattern consisting of white bars over a darker body, to characterize thepigment cells that underlie the white hue. We observe by electron microscopy that cells in white bars are similar to iridophores. In addition, the transcriptomic signature of clownfish white bars exhibits similarities with that of zebrafish iridophores. We further show by pharmacological treatments that these cells are necessary for the white color. Among the top differentially expressed genes in white skin, we identified several genes (fhl2a, fhl2b, saiyan, gpnmb, and apoD1a) and show that three of them are expressed in iridophores. Finally, we show by CRISPR/Cas9 mutagenesis that these genes are critical for iridophore developmentin zebrafish. Our analyses provide clues to the genomic underpinning of color diversity and allow identification of new iridophore genes in fish.

Single cell RNA-seq identifies the origins of heterogeneity in efficient cell transdifferentiation and reprogramming

Author(s) : Francesconi M, Di Stefano B, Berenguer C, de Andrés-Aguayo L, Plana-Carmona M, Mendez-Lago M, Guillaumet-Adkins A, Rodriguez-Esteban G, Gut M, Gut I, Heyn H, Lehner B, Graf T,
Journal : eLife
2019

HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition.

Author(s) : Fiorini F, Robin J, Kanaan J, Borowiak M, Croquette V, Le Hir H, Jalinot P, Mocquet V,
Journal : Nat Commun
2018
Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids. Furthermore, using a single-molecule approach, we show that the sequential interaction of Tax with a RNA-bound UPF1 freezes UPF1: this latter is less sensitive to the presence of ATP and shows translocation defects, highlighting the importance of this feature for NMD. These mechanistic insights reveal how HTLV-1 hijacks the central component of NMD to ensure expression of its own genome.

Evolution of mitotic spindle behavior during the first asymmetric embryonic division of nematodes.

Author(s) : Valfort A, Launay C, Semon M, Delattre M,
Journal : PLoS Biol
2018
Asymmetric cell division is essential to generate cellular diversity. In many animal cells, the cleavage plane lies perpendicular to the mitotic spindle, and it is the spindle positioning that dictates the size of the daughter cells. Although some properties of spindle positioning are conserved between distantly related model species and different cell types, little is known of the evolutionary robustness of the mechanisms underlying this event. We recorded thefirst embryonic division of 42 species of nematodes closely related to Caenorhabditis elegans, which is an excellent model system to study the biophysical properties of asymmetric spindle positioning. Our recordings, corresponding to 128 strains from 27 Caenorhabditis and 15 non-Caenorhabditis species (accessible at http://www.ens-lyon.fr/LBMC/NematodeCell/videos/), constitute a powerful collection of subcellular phenotypes to study the evolution of various cellular processes across species. In the present work, we analyzed our collection to the study of asymmetric spindle positioning. Although all the strains underwent an asymmetric first cell division, they exhibited large intra-and inter-species variations in the degree of cell asymmetry and in several parameters controlling spindle movement, including spindle oscillation, elongation, and displacement. Notably, these parameters changed frequently during evolution with no apparent directionality in the species phylogeny, with the exception of spindle transverse oscillations, which were an evolutionary innovation at the base of the Caenorhabditis genus. These changes were also unrelated to evolutionary variations in embryo size. Importantly, spindle elongation, displacement, and oscillation each evolved independently. This finding contrasts starkly with expectations based on C. elegans studies and reveals previously unrecognized evolutionary changes in spindle mechanics. Collectively, these data demonstrate that, while the essential process of asymmetric cell division has been conserved over the course of nematode evolution, the underlying spindle movement parameters can combine in various ways. Like other developmental processes, asymmetric cell division is subject tosystem drift.

Accurate detection of convergent amino-acid evolution with PCOC.

Author(s) : Rey C, Gueguen L, Semon M, Boussau B,
Journal : Mol Biol Evol
2018
In the history of life, some phenotypes have been acquired several times independently, through convergent evolution. Recently, lots of genome-scale studies have been devoted to identify nucleotides or amino acids that changed ina convergent manner when the convergent phenotypes evolved. These efforts have had mixed results, probably because of differences in the detection methods, andbecause of conceptual differences about the definition of a convergent substitution. Some methods contend that substitutions are convergent only if they occur on all branches where the phenotype changed towards the exact same state at a given nucleotide or amino acid position. Others are much looser in their requirements and define a convergent substitution as one that leads the site at which they occur to prefer a phylogeny in which species with the convergent phenotype group together. Here we suggest to look for convergent shifts in aminoacid preferences instead of convergent substitutions to the exact same amino acid. We define as convergent shifts substitutions that occur on all branches where the phenotype changed and such that they correspond to a change in the type of amino acid preferred at this position. We implement the corresponding model into a method named PCOC. We show on simulations that PCOC better recovers convergent shifts than existing methods in terms of sensitivity and specificity.We test it on a plant protein alignment where convergent evolution has been studied in detail and find that our method recovers several previously identified convergent substitutions and proposes credible new candidates.