Search results for " Gene Expression"

Nucleocytoplasmic transport of the RNA-binding protein CELF2 regulates neural stem cell fates.

2020

The development of the cerebral cortex requires balanced expansion and differentiation of neural stem/progenitor cells (NPCs), which rely on precise regulation of gene expression. Because NPCs often exhibit transcriptional priming of cell-fate-determination genes, the ultimate output of these genes for fate decisions must be carefully controlled in a timely fashion at the post-transcriptional level, but how that is achieved is poorly understood. Here, we report that de novo missense variants in an RNA-binding protein CELF2 cause human cortical malformations and perturb NPC fate decisions in mice by disrupting CELF2 nucleocytoplasmic transport. In self-renewing NPCs, CELF2 resides in the cyt…

Post-transcriptional bursting in genes regulated by small RNA molecules

2018

Gene expression programs in living cells are highly dynamic due to spatiotemporal molecular signaling and inherent biochemical stochasticity. Here we study a mechanism based on molecule-to-molecule variability at the RNA level for the generation of bursts of protein production, which can lead to heterogeneity in a cell population. We develop a mathematical framework to show numerically and analytically that genes regulated post transcriptionally by small RNA molecules can exhibit such bursts due to different states of translation activity (on or off), mostly revealed in a regime of few molecules. We exploit this framework to compare transcriptional and post-transcriptional bursting and also…

2017

AbstractThe evolution of powered flight in insects had major consequences for global biodiversity and involved the acquisition of adaptive processes allowing individuals to disperse to new ecological niches. Flies use both vision and olfactory input from their antennae to guide their flight; chemosensors on fly wings have been described, but their function remains mysterious. We studied Drosophila flight in a wind tunnel. By genetically manipulating wing chemosensors, we show that these structures play an essential role in flight performance with a sex-specific effect. Pheromonal systems are also involved in Drosophila flight guidance: transgenic expression of the pheromone production and d…

Functional impacts of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine at a single hemi-modified CpG dinucleotide in a gene promoter

2017

Abstract Enzymatic oxidation of 5-methylcytosine (5-mC) in the CpG dinucleotides to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxycytosine (5-caC) has central role in the process of active DNA demethylation and epigenetic reprogramming in mammals. However, it is not known whether the 5-mC oxidation products have autonomous epigenetic or regulatory functions in the genome. We used an artificial upstream promoter constituted of one cAMP response element (CRE) to measure the impact of 5-mC in a hemi-methylated CpG on the promoter activity and further explored the consequences of 5-hmC, 5-fC, and 5-caC in the same system. All modifications induced mild impairment of the …

Starvation resistance and tissue-specific gene expression of stress-related genes in a naturally inbred ant population

2016

Starvation is one of the most common and severe stressors in nature. Not only does it lead to death if not alleviated, it also forces the starved individual to allocate resources only to the most essential processes. This creates energetic trade-offs which can lead to many secondary challenges for the individual. These energetic trade-offs could be exacerbated in inbred individuals, which have been suggested to have a less efficient metabolism. Here, we studied the effect of inbreeding on starvation resistance in a natural population of Formica exsecta ants, with a focus on survival and tissue-specific expression of stress, metabolism and immunity-related genes. Starvation led to large tis…

Whi7 is an unstable cell-cycle repressor of the Start transcriptional program

2017

Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional program by G1 CDK-cyclin complexes through the inactivation of Start transcriptional repressors, Whi5 in yeast or Rb in mammals. Here we provide novel keys of how Whi7, a protein related at sequence level to Whi5, represses Start. Whi7 is an unstable protein, degraded by the SCFGrr1 ubiquitin-ligase, whose stability is cell cycle regulated by CDK1 phosphorylation. Importantly, Whi7 associates to G1/S gene promoters in late G1 acting as a repressor of SBF-dependent transcription. Our results demonstrate that Whi7 is a ge…

The cellular growth rate controls overall mRNA turnover, and modulates either transcription or degradation rates of particular gene regulons

2015

We analyzed 80 different genomic experiments, and found a positive correlation between both RNA polymerase II transcription and mRNA degradation with growth rates in yeast. Thus, in spite of the marked variation in mRNA turnover, the total mRNA concentration remained approximately constant. Some genes, however, regulated their mRNA concentration by uncoupling mRNA stability from the transcription rate. Ribosome-related genes modulated their transcription rates to increase mRNA levels under fast growth. In contrast, mitochondria-related and stress-induced genes lowered mRNA levels by reducing mRNA stability or the transcription rate, respectively. We also detected these regulations within th…

Modulation of protein synthesis and degradation maintains proteostasis during yeast growth at different temperatures

2016

To understand how cells regulate each step in the flow of gene expression is one of the most fundamental goals in molecular biology. In this work, we have investigated several protein turnover-related steps in the context of gene expression regulation in response to changes in external temperature in model yeast Saccharomyces cerevisiae. We have found that the regulation of protein homeostasis is stricter than mRNA homeostasis. Although global translation and protein degradation rates are found to increase with temperature, the increase of the catalytic activity of ribosomes is higher than the global translation rate suggesting that yeast cells adapt the amount of translational machinery to…

Limited antibody specificity compromises epitranscriptomic analyses

2019

International audience; A controversial discussion on the occurrence of the RNA modification m1A in mRNA takes a new turn, as an antibody with a central role in modification mapping was shown to also bind mRNA cap structures.

The SCO1731 methyltransferase modulates actinorhodin production and morphological differentiation of Streptomyces coelicolor A3(2)

2018

AbstractStreptomyces coelicolor is a Gram-positive microorganism often used as a model of physiological and morphological differentiation in streptomycetes, prolific producers of secondary metabolites with important biological activities. In the present study, we analysed Streptomyces coelicolor growth and differentiation in the presence of the hypo-methylating agent 5′-aza-2′-deoxycytidine (5-aza-dC) in order to investigate whether cytosine methylation has a role in differentiation. We found that cytosine demethylation caused a delay in spore germination, aerial mycelium development, sporulation, as well as a massive impairment of actinorhodin production. Thus, we searched for putative DNA…