Biology subjects

Benchouaia, M.

Publications and source records attributed to Benchouaia, M..

4 recordsLinked to original sources

bioRxiv2026

Shining a light on the dark Nt-acetylome by integrating omics data

N-terminal acetylation, catalysed by N-terminal acetyltransferases (Nats), is one of the most prevalent protein modifications and is implicated in human diseases. Yet, despite extensive COFRADIC-based proteomics, only [~]5-10% of the proteome has been interrogated, leaving the majority of the Nt-acetylome unexplored. Here, we combined all major COFRADIC datasets with sel-TRAP, a high-sensitivity, orthogonal approach for profiling co-translational Nat targets via selective ribosome purification. This integrated analysis refined the substrate specificities of NatA, NatB, and NatC/E/F and provided the most comprehensive view to date of the canonical human and yeast Nt-acetylomes. Importantly, we also uncovered hundreds of cryptic Nat substrates arising from alternative translation initiation, with unexpected Nt-proteoforms constituting a previously underappreciated source of Nat targets. Collectively, our results revealed the complex landscape of a "dark" Nt-acetylome, the characterization of which, including its functional roles in regulating protein function and in disease, remains a major challenge for future research.

genomics↗

bioRxiv2023

Transcriptomic landscape of posterior regeneration in the annelid Platynereis dumerilii

Background: Restorative regeneration, the capacity to reform a lost body part following amputation or injury, is an important and still poorly understood process in animals. Annelids, or segmented worms, show amazing regenerative capabilities, and as such are a crucial group to investigate. Elucidating the molecular mechanisms that underpin regeneration in this major group remains a key goal. Among annelids, the nereididae Platynereis dumerilii (re)emerged recently as a front-line regeneration model. Following amputation of its posterior part, Platynereis worms can regenerate both differentiated tissues of their terminal part as well as a growth zone that contains putative stem cells. While this regeneration process follows specific and reproducible stages that have been well characterized, the transcriptomic landscape of these stages remains to be uncovered. Results: We generated a high quality de novo Reference transcriptome for the annelid Platynereis dumerilii. To do so, we produced and analyzed three RNA-sequencing datasets, encompassing five stages of posterior regeneration, along with blastema stages and non-amputated tissues as controls. We included these regeneration RNA-seq datasets, as well as embryonic and tissue-specific datasets from the literature to produce a Reference transcriptome. We used this Reference transcriptome to perform in depth analyzes of RNA-seq data during the course of regeneration to reveal the important dynamics of the gene expression, process with thousands of genes differentially expressed between stages, as well as unique and specific genes expression at each regeneration stage. The study of these genes highlighted the importance of the nervous system at both early and late stages of regeneration, as well as the enrichment of RNA-binding proteins (RBPs) during almost the entire regeneration process. Conclusions: In this study, we provided a high-quality de novo Reference transcriptome for the annelid Platynereis that is useful for investigating various developmental processes, including regeneration. Our extensive stage-specific transcriptional analysis during the course of posterior regeneration shed light upon major molecular mechanisms and pathways, and will foster many specific studies in the future.

genomics↗

bioRxiv2022

Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import.

N-terminal ends of polypeptides are critical for the selective co-translational recruitment of N-terminal modification enzymes. However, it is unknown whether specific N-terminal signatures differentially regulate protein fate according to their cellular functions. In this work, we developed an in-silico approach to detect functional preferences in cellular N-terminomes, and identified in S. cerevisiae more than 200 Gene Ontology terms with specific N-terminal signatures. In particular, we discovered that Mitochondrial Targeting Sequences (MTS) show a strong and specific over-representation at position 2 of hydrophobic residues known to define potential substrates of the N-terminal acetyltransferase NatC. We validated mitochondrial precursors as co-translational targets of NatC by selective purification of translating ribosomes, and found that their N-terminal signature is conserved in Saccharomycotina yeasts. Finally, systematic mutagenesis of the position 2 in a prototypal yeast mitochondrial protein confirmed its critical role in mitochondrial protein import. Our work highlights the hydrophobicity of MTS N-terminal residues and their modification by NatC as critical features for the definition of the mitochondrial proteome, providing a molecular explanation for mitochondrial defects observed in yeast or human NatC-depleted cells. Functional mapping of N-terminal residues thus has the potential to support the discovery of novel mechanisms of protein regulation or targeting.

genomics↗

bioRxiv2020

The impact of transposable elements on tomato diversity

Tomatoes come in a multitude of shapes and flavors despite a narrow genetic pool. Here, we leveraged whole-genome resequencing data available for 602 cultivated and wild accessions to determine the contribution of transposable elements (TEs) to tomato diversity. We identified 6,906 TE insertions polymorphisms (TIPs), which result from the mobilization of 337 distinct TE families. Most TIPs are low frequency variants and disproportionately located within or adjacent to genes involved in environmental response. In addition, we show that genic TE insertions tend to have strong transcriptional effects and can notably lead to the generation of multiple transcript isoforms. We also uncovered through genome-wide association studies (GWAS) ~180 TIPs associated with extreme variations in major agronomic traits or secondary metabolites. Importantly, these TIPs tend to affect loci that are distinct from those tagged by SNPs. Collectively, our findings suggest a unique and important role for TE mobilization in tomato diversification, with important implications for future breeding.

plant biology↗