Biology subjects

Brun, C.

Publications and source records attributed to Brun, C..

24 records · Page 2Linked to original sources

bioRxiv2020

GLI3 Processing by the Primary Cilium Regulates Muscle Stem Cell Entry into GAlert

Satellite cells are required for the growth, maintenance, and regeneration of skeletal muscle. Quiescent satellite cells possess a primary cilium, a structure that regulates the processing of the GLI family of transcription factors. Here we find that GLI3, specifically, plays a critical role in satellite cell activation. Primary cilia-mediated processing of GLI3 is required to maintain satellite cells in a G0 dormant state. Strikingly, satellite cells lacking GLI3 enter GAlert in the absence of injury. Furthermore, GLI3 depletion or inhibition of its processing stimulates symmetrical division in satellite cells and expansion of the stem cell pool. As a result, satellite cells lacking GLI3 display rapid cell-cycle entry, increased proliferation and augmented self-renewal, and markedly enhanced long-term regenerative capacity. Therefore, our results reveal an essential role for primary cilia processing of GLI3 in regulating muscle stem cell activation and fate.

cell biology↗

bioRxiv2020

MetamORF: A repository of unique short Open Reading Frames identified by both experimental and computational approaches for gene-level and meta-analysis

The development of high-throughput technologies revealed the existence of non-canonical short open reading frames (sORFs) on most eukaryotic RNAs. They are ubiquitous genetic elements highly conserved across species and suspected to be involved in numerous cellular processes. MetamORF (http://metamorf.hb.univ-amu.fr/) aims to provide a repository of unique sORFs identified in the human and mouse genomes with both experimental and computational approaches. By gathering publicly available sORF data, normalizing it and summarizing redundant information, we were able to identify a total of 1,162,675 unique sORFs. Despite the usual characterization of ORFs as short, upstream or downstream, there is currently no clear consensus regarding the definition of these categories. Thus, the data has been reprocessed using a normalized nomenclature. MetamORF enables new analyses at loci, gene, transcript and ORF levels, that should offer the possibility to address new questions regarding sORF functions in the future. The repository is available through an user-friendly web interface, allowing easy browsing, visualization, filtering over multiple criteria and export possibilities. sORFs could be searched starting from a gene, a transcript, an ORF ID, or looking in a genome area. The database content has also been made available through track hubs at UCSC Genome Browser.

bioinformatics↗

bioRxiv2019

The role of 3’UTR-protein complexes in the regulation of protein multifunctionality and subcellular localization

Multifunctional proteins often perform their different functions when localized in different subcellular compartments. However, the mechanisms leading to their localization are largely unknown. Recently, 3UTRs were found to regulate the cellular localization of newly synthesized proteins through the co-translational formation of 3UTR-protein complexes. Here, we investigate the formation of 3UTR-protein complexes involving multifunctional proteins by exploiting large-scale protein-protein and protein-RNA interaction networks. Focusing on 238 human extreme multifunctional (EMF) proteins, we predicted 1411 3UTR-protein complexes involving 128 EMF proteins and evaluated their role in regulating protein cellular localization and multifunctionality. Notably, we find that EMF proteins lacking localization addressing signals, yet present at both the nucleus and cell surface, often form 3UTR-protein complexes. In addition, they provide EMF proteins with the diversity of interaction partners necessary to their multifunctionality. Archetypal moonlighting proteins are also predicted to form 3UTR-protein complexes thereby reinforcing our findings. Finally, our results indicate that the formation of 3UTR-protein complex may be a common phenomenon in human cells, affecting up to 20% of the proteins in the human interactome.

systems biology↗

bioRxiv2018

Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with MEI4

Programmed formation of DNA double strand breaks (DSBs) initiates the meiotic homologous recombination pathway. This pathway allows homologous chromosomes to find each other and the formation of crossing overs, the products of reciprocal exchanges, which are required for proper chromosome segregation at the first meiotic division. Meiotic DSBs are catalyzed by Spo11 that forms a complex with a second subunit, TopoVIBL, and mediates a DNA type II topoisomerase-like cleavage. Several other proteins are essential for meiotic DSB formation, including three evolutionarily conserved proteins first identified in Saccharomyces cerevisiae (Mer2, Mei4 and Rec114). These three S. cerevisiae proteins and their mouse orthologs (IHO1, MEI4 and REC114) co-localize on the axes of meiotic chromosomes, and mouse IHO1 and MEI4 are essential for meiotic DSB formation. Here, we show that mouse Rec114 is required for meiotic DSB formation. Moreover, MEI4 forms a complex with REC114 and IHO1 in mouse spermatocytes, consistent with cytological observations. We then demonstrated in vitro the formation of a stable complex between REC114 C-terminal domain and MEI4 N-terminal domain. We further determine the structure of REC114 N-terminal domain that revealed similarity with Pleckstrin Homology domains and its property to dimerize. These analyses provide direct insights into the architecture of these essential components of the meiotic DSB machinery.

molecular biology↗

bioRxiv2018

Generation of a versatile BiFC ORFeome library for analyzing protein-protein interactions in live Drosophila

Transcription factors achieve specificity by establishing intricate interaction networks that will change depending on the cell context. Capturing these interactions in live condition is however a challenging issue that requires sensitive and non-invasive methods. We present a set of fly lines, called \"multicolor BiFC library\", which covers most of the Drosophila transcription factors for performing Bimolecular Fluorescence Complementation (BiFC). The multicolor BiFC library can be used to probe binary or tripartite interactions and is compatible for large-scale interaction screens. The library can also be coupled with established Drosophila genetic resources to analyze interactions in the developmentally relevant expression domain of each protein partner. We provide proof of principle experiments of these various applications, using Hox proteins in the live Drosophila embryo as a case study. Overall this novel collection of ready-to-use fly lines constitutes an unprecedented genetic toolbox for the identification and analysis of protein-protein interactions in vivo.

genomics↗

bioRxiv2016

Perturbed human sub-networks by Fusobacterium nucleatum candidate virulence factors

F. nucleatum is a gram-negative anaerobic species residing in the oral cavity and implicated in several inflammatory processes in the human body. Although F. nucleatum abundance is increased in inflammatory bowel disease subjects and is prevalent in colorectal cancer patients, the causal role of the bacterium in gastrointestinal disorders and the mechanistic details of host cell functions subversion are not fully understood.\n\nWe devised a computational strategy to identify putative secreted F. nucleatum proteins (FusoSecretome) and to infer their interactions with human proteins based on the presence of host molecular mimicry elements. FusoSecretome proteins share similar features with known bacterial virulence factors thereby highlighting their pathogenic potential. We show that they interact with human proteins that participate in infection-related cellular processes and localize in established cellular districts of the host-pathogen interface. Our network-based analysis identified 31 functional modules in the human interactome preferentially targeted by 138 FusoSecretome proteins, among which we selected 26 as main candidate virulence proteins, representing both putative and known virulence proteins. Finally, 6 of the preferentially targeted functional modules are implicated in the onset and progression of inflammatory bowel diseases and colorectal cancer.\n\nOverall, our computational analysis identified candidate virulence proteins potentially involved in the F. nucleatum - human cross-talk in the context of gastrointestinal diseases.

bioinformatics↗