Biology subjects

Larue, A.

Publications and source records attributed to Larue, A..

4 recordsLinked to original sources

bioRxiv2024

Hao-Fountain syndrome protein USP7 controls neuronal differentiation via BCOR-ncPRC1.1

Pathogenic variants in the ubiquitin-specific protease 7 (USP7) gene cause a neurodevelopmental disorder called Hao-Fountain syndrome. However, which of USP7s pleiotropic functions are relevant for neurodevelopment remains unclear. Here, we present a combination of quantitative proteomics, transcriptomics and epigenomics to define the USP7 regulatory circuitry during neuronal differentiation. USP7 activity is required for the transcriptional programs that direct both differentiation of embryonic stem cells into neural stem cells, and the neuronal differentiation of SH-SY5Y neuroblastoma cells. USP7 controls the dosage of the Polycomb H2AK119ub1 ubiquitin ligase complexes ncPRC1.1 and ncPRC1.6. Loss-of-function experiments revealed that BCOR-ncPRC1.1, but not ncPRC1.6, is a key effector of USP7 during neuronal differentiation. Indeed, BCOR-ncPRC1.1 mediates a major portion of USP7-dependent gene regulation during this process. Besides providing a detailed map of the USP7 regulome during neurodifferentiation, our results suggest that USP7 and ncPRC1.1-associated neurodevelopmental disorders involve dysregulation of a shared epigenetic network.

molecular biology↗

bioRxiv2024

Transposable elements as evolutionary driving force to ecological speciation in cactophilic Drosophila species

Host shifts in insects have been considered a key process with the potential to contribute to reproductive isolation and speciation. Both genomics and transcriptomics variation have been attributed to such a process, in which gene families with functions associated with host localization, acceptance, and usage have been proposed to evolve. In this context, cactophilic Drosophila species are an excellent model to study host shift evolution, since they use a wide range of cacti as hosts, and many species have different preferences. Transposable elements are engines of genetic novelty between populations and species, driving rapid adaptive evolution. However, the extent of TEs contribution to host shift remains unexplored. We performed genomic and transcriptomic analyses in six genomes of cactophilic species/subspecies to investigate how TEs interact with genes associated with host shift. Our results revealed enrichment of TEs at promoter regions of host shift-related genes, with [~]39% of the odorant receptors containing their transcription factor binding sites within TEs. We observed that [~]50% of these TEs are Helitrons, demonstrating an unprecedented putative cis-regulatory role of Helitrons in Drosophila. Differential expression analysis between species with different preferred hosts revealed divergence in gene expression in head and larval tissues. Although TEs presence does not affect overall gene expression, we observed 6.27% of the expressed genes generating gene-TE chimeric transcripts, including those with function affecting host preference. Our combined genomic and transcriptomic approaches provide evidence of TE-driven divergence between species, highlighting the evolutionary role of TEs in the context of host shift, a key adaptive process that can cause reproductive isolation.

evolutionary biology↗

bioRxiv2024

Intricate interactions between antiviral immunity and transposable element control in Drosophila

Transposable elements (TEs) are parasite DNA sequences that are controlled by RNA interference pathways in many organisms. In insects, antiviral immunity is also achieved by the action of small RNAs. In the present study, we analyzed the impacts of an infection with Drosophila C Virus (DCV) and found that TEs are involved in a dual response: on the one hand TE control is released upon DCV infection, and on the other hand TE transcripts help the host reduce viral replication. This discovery highlights the intricate interactions in the arms race between host, genomic parasites, and viral pathogens. Significance statementTransposable elements (TEs) are widespread components of all genomes. They were long considered as mere DNA parasites but are now acknowledged as major sources of genetic diversity and phenotypic innovations. Using Drosophila C virus, here we show that TEs are at the center of defense and counter-attack between host and virus. On the one hand, TE control is released upon viral infection, and on the other hand, TE transcripts help the host reduce viral replication. To our knowledge, this is the first time such a complex host-pathogen interaction involving TEs is shown.

evolutionary biology↗

bioRxiv2022

ChimeraTE: A pipeline to detect chimeric transcripts derived from genes and transposable elements

Transposable elements (TEs) produce structural variants and are considered an important source of genetic diversity. Notably, TE-gene fusion transcripts, i.e., chimeric transcripts, have been associated with adaptation in several species. However, the identification of these chimeras remains hindered due to the lack of detection tools at a transcriptome-wide scale, and to the reliance on a reference genome, even though different individuals/cells/strains have different TE insertions. Therefore, we developed ChimeraTE, a pipeline that uses paired-end RNA-seq reads to identify chimeric transcripts through two different modes. Mode 1 is the reference-guided approach that employs canonical genome alignment, and Mode 2 identifies chimeras derived from fixed or insertionally polymorphic TEs without any reference genome. We have validated both modes using RNA-seq data from four Drosophila melanogaster wild-type strains. We found [~]1.12% of all genes generating chimeric transcripts, most of them from TE-exonized sequences. Approximately [~]23% of all detected chimeras were absent from the reference genome, indicating that TEs belonging to chimeric transcripts may be recent, polymorphic insertions. ChimeraTE is the first pipeline able to automatically uncover chimeric transcripts without a reference genome, consisting of two running Modes that can be used as a tool to investigate the contribution of TEs to transcriptome plasticity.

bioinformatics↗