Biology subjects

Picard, M.-E.

Publications and source records attributed to Picard, M.-E..

3 recordsLinked to original sources

bioRxiv2024

HEPN-AbiV is an RNase in the antiphage system AbiV

Prokaryotes and eukaryotes possess defense systems, which can be either innate or acquired, to protect against viral infections. At the bacterial population level, abortive infection (Abi) serves as an innate immune defense mechanism against phage invasion. The AbiV antiviral system is prevalent in several bacterial genomes and exhibits diverse characteristics in terms of gene composition and evolution. Our investigation into the Lactococcus AbiV system revealed a novel two-component system, abiV1 and abiV2, both of which are essential for its function as a type III toxin-antitoxin system. The toxin component AbiV (product of abiV1) is an RNase belonging to the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding) superfamily as it carries the consensus Rx4-6H motif. In vivo assays coupled with mass spectrometry showed that the lactococcal AbiV was expressed in the presence or absence of phages while in vitro experiments demonstrated that AbiV1 degraded ribosomal RNA but not mRNA. On the other hand, the antitoxin component (abiV2) was found to function as an RNA molecule that inhibited the nuclease activity of the AbiV1 toxin. The structural characterization of AbiV revealed that this RNase utilizes a large patch of positively charged area across the dimer to anchor RNA molecules. In addition, we showed that the AbiV N-terminal region (amino acids 1 to 23) is crucial for its RNase activity as a truncated AbiV lacking this segment adopted distinct conformational states incompatible with RNA binding. This study provided novel insights into the mode of action of the antiviral system AbiV.

biochemistry↗

bioRxiv2024

Compensatory mutations potentiate constructive neutral evolution by gene duplication

Protein functions generally depend on their assembly into complexes. During evolution, some complexes have transitioned from homomers encoded by a single gene to heteromers encoded by duplicate genes. This transition could occur without adaptive evolution through intermolecular compensatory mutations. Here, we experimentally duplicate and evolve an homodimeric enzyme to examine if and how this could happen. We identify hundreds of deleterious mutations that inactivate individual homodimers but produce functional enzymes when co-expressed as duplicated proteins that heterodimerize. The structure of one such heteromer reveals how both losses of function are buffered through the introduction of asymmetry in the complex that allows them to subfunctionalize. Constructive neutral evolution can thus occur by gene duplication followed by only one deleterious mutation per duplicate. One sentence summaryCompensatory deleterious mutations entangle gene duplicates

evolutionary biology↗

bioRxiv2023

Facial expression is a distinctive behavioural marker of pain processing in the brain

Pain is a private experience observable through various verbal and non-verbal behavioural manifestations, each of which may relate to different pain-related functions. Despite the importance of understanding the cerebral mechanisms underlying those manifestations, there is currently limited knowledge on the neural correlates of the facial expression of pain. In this functional magnetic resonance imaging (fMRI) study, noxious heat stimulation was applied in healthy volunteers and we tested if previously published brain signatures of pain were sensitive to pain expression. We then applied a multivariate pattern analysis to the fMRI data to predict the facial expression of pain. Results revealed the inability of previously developed pain neurosignatures to predict the facial expression of pain. We thus propose a Facial Expression of Pain Signature (FEPS) conveying distinctive information about the brain response to nociceptive stimulations with minimal or no overlap with other pain-relevant brain signatures associated with nociception, pain ratings, thermal pain aversiveness, or pain valuation. The FEPS may provide a distinctive functional characterization of the distributed cerebral response to nociceptive pain associated with the socio-communicative role of non-verbal pain expression. This underscores the complexity of pain phenomenology by reinforcing the view that neurosignatures conceived as biomarkers must be interpreted in relation to the specific pain manifestation(s) predicted and their underlying function(s). Future studies should explore other pain-relevant manifestations and assess the specificity of the FEPS against simulated pain expressions and other types of aversive or emotional states.

neuroscience↗