Biology subjects

Morellet, N.

Publications and source records attributed to Morellet, N..

8 recordsLinked to original sources

bioRxiv2026

Pho92 direct interaction with Not1 recruits the CCR4-NOT complex to m6A containing mRNAs to modulate meiosis in S. cerevisiae

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNAs. In S. cerevisiae, m6A is exclusively deposited during meiosis, where it plays an essential role in meiotic progression. In this context, the absence of Pho92, the sole known m6A-binding protein in budding yeast, leads to the abnormal persistence of m6A-containing mRNAs, ultimately resulting in delayed meiosis. Here, we investigate how m6A recognition by Pho92 regulates gene expression. Using complementary in vivo and in vitro approaches, we identify direct interactions between Pho92 and Not1, the scaffold subunit of the CCR4-NOT deadenylase complex. Structural analyses reveal that a short evolutionarily conserved motif in Pho92 adopts an -helical conformation that docks onto specific regions of Not1. Functionally, these interactions are required for efficient meiotic progression. Altogether, our findings demonstrate that Pho92 couples m6A recognition to the main deadenylase to shape the meiotic transcriptome. More broadly, our work provides mechanistic insights into how epitranscriptomic signals interface with the core mRNA decay machinery to regulate gene expression during cellular differentiation.

molecular biology↗

bioRxiv2024

Metal sensing properties of the disordered loop from the Arabidopsis metal transceptor IRT1

The plant IRT1 iron transporter is a plasma membrane protein that takes up iron in root upon iron-limited conditions. Besides its primary metal substrate iron, IRT1 also transports other divalent metals that overaccumulate in plants when soil iron is low and IRT1 is highly expressed. We previously reported that the intracellular regulatory loop between transmembrane helices TM4 and TM5, comprising IRT1 residues from 144 to 185, is involved in the post-translational regulation of IRT1 by its non-iron metal substrates. Upon excess of zinc, IRT1 (144-185) undergoes phosphorylation by the CIPK23 kinase followed by its ubiquitination by IDF1 to target IRT1 for vacuolar degradation. This zinc-dependent downregulation of IRT1 requires the presence of four histidine (H) residues in IRT1 loop, that directly bind zinc. However, how selective metal binding is achieved and how this allows downstream regulation to take place is largely unknown. Here, we characterized the metal binding properties and structure of IRT1 loop to better understand the molecular basis of non-iron metal sensing and signaling. Using a combination of circular dichroism and NMR, we demonstrate that zinc and manganese bind to IRT1 loop with nanomolar range affinity, and that metal binding does not trigger structuration of the loop. We prove that zinc and manganese binding is mediated by the four H residues and identify aspartic acid (D) residue D173 as helping in metal coordination and participating to metal sensing and metal-dependent degradation of IRT1 in plants. Altogether, our data provide further evidence of how the regulatory loop of IRT1 senses high cytosolic divalent metal concentrations to regulate metal uptake in plants.

plant biology↗

bioRxiv2023

Assessing bias and robustness of social network metrics using GPS based radio-telemetry data

O_LISocial network analysis of animal societies allows scientists to test hypotheses about social evolution, behaviour, dynamical processes, and transmission events such as the spread of disease. However, the accuracy of estimated social network metrics depends on the proportion of individuals sampled, actual sample size, and frequency of observations. Robustness of network metrics derived from a sample has thus far been examined through various simulation studies. However, simulated data do not necessarily reflect the nuances of real empirical data. C_LIO_LIWe used some of the largest available GPS telemetry relocation datasets from five species of ungulates characterised by different behavioural and ecological traits and living in distinct environmental contexts to study the bias and robustness of social network metrics. We introduced novel statistical methods to quantify the uncertainty in network metrics obtained from a partial population suited to autocorrelated data such as telemetry relocations. We analysed how social network metrics respond to down-sampling from the observed data and applied pre-network data permutation techniques, a bootstrapping approach, correlation, and regression analyses to assess the stability of network metrics when based on samples of a population. C_LIO_LIWe found that global network metrics like density remain robust when the sample size is lowered, whereas some local network metrics, such as eigenvector centrality, are entirely unreliable when a large proportion of the population is not monitored. We show how to construct confidence intervals around the point estimates of these metrics representing the uncertainty as a function of the number of nodes in the network. C_LIO_LIOur uncertainty estimates enable the statistical comparison of social network metrics under different conditions, such as analysing daily and seasonal changes in the density of a network. Despite the striking differences in the ecology and sociality among the five different ungulate species, the various social network metrics behave similarly under downsampling, suggesting that our approach can be applied to a wider range of species across vertebrates. Our methods can guide methodological decisions about animal social network research (e.g., sampling design and sample sizes) and allow more accurate ecological inferences from the available data. C_LI

animal behavior and cognition↗

bioRxiv2023

Reproductive tactics, birth timing and the trade-off between risk avoidance and foraging in an income breeder

The behavioural trade-off between foraging and risk avoidance is expected to be particularly acute during gestation and lactation, when the energetic demands of reproduction peak. We investigated how female roe deer, an income breeding ungulate, adjust their management of this trade-off during the birth period in terms of foraging activity and habitat use. We showed that activity levels of reproductive females more than doubled immediately following parturition, when energy demand is highest. Moreover, reproductive females increased their use of open habitat during daytime and ranged closer to roads, but slightly further from refuge woodland, compared to non-reproductive females. However, these post-partum modifications in behaviour were particularly pronounced in late-parturient females who adopted a more risk prone tactic, presumably to compensate for the fitness handicap of their late-born offspring. In income breeders, individuals that give birth late may be forced to trade risk avoidance for resource acquisition during peak allocation to reproduction, likely with significant fitness consequences.

animal behavior and cognition↗

bioRxiv2023

Using accelerometers to infer behaviour of cryptic species in the wild

Accelerometery is revolutionising the field of behavioural ecology through its capacity to detect the fine-scale movements of animals resulting from their behaviour. Because it is often difficult to infer the behaviour of wildlife on a continuous basis, particularly for cryptic species, accelerometers potentially provide powerful tools for remote monitoring of their behavioural responses to the environment. The goal of this study was to provide a detailed, calibrated methodology, including practical guidelines, to infer the behaviour of free-ranging animals from acceleration data. This approach can be employed to reliably infer the time budget of species that are difficult to observe in certain environments or at certain times of the day. To this end, we trained several behavioural classification algorithms with accelerometer data obtained on captive roe deer, then validated these algorithms with data obtained on free-ranging roe deer, and finally predicted the time-budgets of a substantial sample of unobserved free-ranging roe deer in a human-dominated landscape. The best classification algorithm was the Random Forest which predicted five behavioural classes with a high overall level of accuracy ({approx} 90%). Except for grooming (34-38%), we were able to predict the behaviour of free-ranging roe deer over the course of a day with high accuracy, in particular, foraging head down, running, walking and immobile (68-94%). Applied to free-ranging individuals, the classification allowed us to estimate, for example, that roe deer spent about twice as much time foraging head-down, walking or running during dawn and dusk than during daylight or night-time. By integrating step by step calibration and validation of accelerometer data prior to application in the wild, our approach is transferable to other free-ranging animals for predicting key behaviours in cryptic species.

animal behavior and cognition↗

bioRxiv2022

Body mass change over winter is consistently sex-specific across roe deer populations

In most polygynous vertebrates, males must allocate energy to growing secondary sexual characteristics, such as ornaments or weapons, that they require to attract and defend potential mates, impacting body condition and potentially entailing fitness costs. We investigated sex differences in over winter body mass change across five intensively monitored populations of roe deer (Capreolus capreolus) with markedly contrasting environmental conditions. At winter onset, males weighed, on average, 8.4% (from 4.7% in the most northerly population to 11.6% in the most southerly one) more than females. However, across all populations, males fared worse over the winter than females, losing more (Sweden) or gaining less (France) mass, so that sexual mass dimorphism was virtually absent prior to the onset of spring. Our findings reveal that the direction of over-winter change in mass of roe deer depends on winter severity, but that males are consistently more sensitive to this environmental constraint than females. As a result of this sex-specific change in body mass, sexual mass dimorphism is lowest at the onset of the territorial season. We suggest that allocation to antler growth and territory establishment drives this pattern, providing a likely explanation to account for the lower rates of male adult survival that are consistently reported in this weakly dimorphic species.

ecology↗

bioRxiv2020

Structural and dynamic characterization of the C-terminal tail of ErbB2: disordered but not random

ErbB2 (or HER2) is a receptor tyrosine kinase overexpressed in some breast cancers, associated with poor prognosis. Treatments targeting the receptor extracellular and kinase domains have greatly improved disease outcome in the last twenty years. In parallel, the structures of these domains have been described, enabling better mechanistic understanding of the receptor function and targeted inhibition. However, ErbB2 disordered C-terminal cytoplasmic tail (CtErbB2) remains very poorly characterized in terms of structure, dynamics and detailed functional mechanism. Yet, it is where signal transduction is triggered, via phosphorylation of tyrosine residues, and carried out, via interaction with adaptor proteins. Here we report the first description of ErbB2 disordered tail at atomic resolution, using NMR and SAXS. We show that although no part of CtErbB2 has any stable secondary or tertiary structure, it has around 20% propensity for a N-terminal helix that is suspected to interact with the kinase domain, and many PPII stretches distributed all along the sequence, forming potential SH3 and WW domains binding sites. Moreover, we identified a long-range transient contact involving CtErbB2 termini. These characteristics suggest new potential mechanisms of auto-regulation and protein-protein interaction. SIGNIFICANCEWe report here the first description of the receptor tyrosine kinase ErbB2 disordered tail (CtErbB2) at atomic resolution, using NMR and SAXS. We show that although CtErbB2 exhibits no stable structure, it does exhibit partial secondary and tertiary structures likely important for its function. These structural elements are consistent with an active role of the C-terminal tail in the regulation of the receptors activity, thanks to the presence of preformed structures for intramolecular interactions, as well as long-range contacts modulating accessibility of those sites and proline interaction sites distinct from the main tyrosine sites. Together, those results reinforce the view that disordered tails of receptors are more than random anchors for partners.

biophysics↗

bioRxiv2018

Fluctuating pathogen-mediated selection drives the maintenance of innate immune gene polymorphism in a widespread wild ungulate

Toll-like Receptors (TLR) play a central role in recognition and host frontline defence against a wide range of pathogens. A number of recent studies have shown that TLR genes (Tlrs) often exhibit a large polymorphism in natural populations. Yet, there is little knowledge on how this polymorphism is maintained and how it influences disease susceptibility in the wild. In a previous work, we showed that some Tlrs exhibit similarly high levels of genetic diversity than Mhc and contemporary signatures of balancing selection in roe deer (Capreolus capreolus), an abundant and widespread ungulate in Europe. Here, we tested whether Mhc-Drb or Tlr (Tlr2, Tlr4 and Tlr5) diversity is driven by pathogen-mediated selection. We examined the relationships between their genotype (heterozygosity status and presence of specific alleles) and infections with Toxoplasma and Chlamydia, two intracellular pathogens known to cause reproductive failure in ungulates. We showed that Toxoplasma and Chlamydia exposures vary significantly across year and landscape structure with few co-infection events detected, and that the two pathogens act antagonistically on Tlr2 polymorphism. By contrast, we found no evidence of association with Mhc-Drb and a limited support for Tlr heterozygosity advantage. Our study confirmed the importance of looking beyond Mhc genes in wildlife immunogenetic studies. It also emphasized the necessity to consider multiple pathogen challenges and their spatiotemporal variation to improve our understanding of vertebrate defence evolution against pathogens.

evolutionary biology↗