Biology subjects

MARTIN, J.-R.

Publications and source records attributed to MARTIN, J.-R..

5 recordsLinked to original sources

bioRxiv2026

Pseudouridylation of rRNA by specific snoRNA disrupts ribosomal machinery and consequently affects metabolism, longevity and neurodegeneration

In our society, ageing, longevity, and neurodegenerative diseases are major concerns of public health. Recently, in Drosophila, we have identified a new cluster of three snoRNAs, including jouvence, and showed that each of them affect longevity and neurodegeneration. As these snoRNAs are required in the epithelium of the gut, these results point-out a causal relationship between the epithelium of the gut and the neurodegenerative lesions through the metabolic parameters, indicating a gut-brain axis. Here, we demonstrate that each snoRNA pseudouridylates a specific site on ribosomal-RNA, which consequently affects the amount of ribosomes as well as the translational efficacy. Moreover, using TRAP experiment assay, we also show that these lacks of pseudouridylations modify the translation of specific genes involved in lipid metabolism. Consequently, these lead to a chronic deregulation of trigycerides and sterols levels, whose correlate to an increase of neurogenerative lesions in old flies, as well as to a modification of longevity.

neuroscience↗

bioRxiv2025

A cluster of three snoRNAs including jouvence required in the gut determines lifespan and confers neuroprotection through metabolic parameters

In our society, the aging of the population is a major concern of public health. Recently we have identified a new snoRNA (jouvence) in Drosophila, and showed that its deletion (F4) reduces lifespan, while its overexpression increases it. F4 deleted flies also present neurodegenerative lesions and a deregulation of metabolic parameters as triglycerides and sterol. However, a deeper characterization of this genomic locus has revealed the presence of two other snoRNAs. Here, we have characterized at the whole organismal level, the role of each them. First, we show that each snoRNAs are expressed in the epithelium of the gut (enterocytes), and in the fat body. Second, in F4 deletion, the re-expression of each snoRNA in the enterocytes or in the fat body is sufficient to improve lifespan, and protect against neurodegeneration in old flies. In addition, depending of the snoRNAs, it rescues the expression of specific deregulated genes within the epithelium of the gut, involved in lipids and sterol metabolism. Consequently, these two metabolic parameters are also rescued, establishing a relationship between the lesions of the brain, the metabolic disorders, the lifespan, and each snoRNAs respectively. Finally, histological stainings as Nile Red and BODIPY C11-581/591 have revealed that the neurodegenerative lesions are due to an increase of free sterol within the brain, and lipid peroxydation in the pericerebral fat body. Altogether, these results point-out a causal relationship between the epithelium of the gut and the neurodegenerative lesions through the metabolic parameters, indicating a gut-brain axis.

neuroscience↗

bioRxiv2024

The knockdown of the snoRNA-jouvence blocks the cell proliferation and leads to cell death of human primary cancerous glioblastoma cells

Cancer research aims to identify new therapeutic targets and provide patients with more effective therapies that generate fewer deleterious side effects. Previous studies have demonstrated the role of small nucleolar RNAs (snoRNAs) in many physiological and pathological cellular processes, including cancers. SnoRNAs are a group of non-coding RNAs involved in different post-transcriptional modifications of ribosomal RNAs. Recently, we have identified a new snoRNA, named jouvence (snoRNA-jou) in humans. Here, we characterize the effect of the knockdown of the snoRNA-jouvence by sh-lentivirus on human primary glioblastoma cells. The sh-lentivirus induces a significant decrease of cell proliferation, proportional to the amount of lentivirus used. For example, with a MOI-20, a decrease of more than 50% is observed after only 72 hours, and even up to 80% after 10 days. Moreover, a EdU proliferative test confirms this decrease in cell proliferation, while a TUNEL test reveals the presence of apoptotic cells. A RNA-Seq analysis, validated by RT-qPCR, reveals that the snoRNA-jou knockdown induces a significant deregulation of several key genes involved in the cell cycle regulation, such as cyclins B1, A2 and p21, indicating a cell cycle blockage. Altogether, these results allow hypothesising that the knockdown of the snoRNA-jouvence could potentially be use as a new anti-cancer treatment (sno-Therapy).

cancer biology↗

bioRxiv2020

ninaD regulates cholesterol homeostasis from the midgut which protects against neurodegeneration

Cholesterol is crucial to maintain normal cellular function. In human, it has also been involved in various neurodegeneration processes, as Niemann-Pick and Alzheimer diseases. Recently, we have identified a small nucleolar RNA (jouvence) required in the epithelial cells of the gut (enterocytes), and showed that its overexpression extends lifespan. A transcriptomic analysis has revealed a deregulation of several genes in jouvence mutants. Among them, ninaD encoding a mammalian homolog to class B Scavenger receptor is importantly upregulated. In Drosophila, ninaD is required for the uptake of the dietary carotenoid, used for the formation of rhodopsin. Here, we show that jouvence-deleted flies are deficient in cholesterol-ester, as well as old flies present neurodegenerative lesions. Restoring ninaD mRNA expression level in enterocytes restores the metabolic cholesterol-ester level, prevents neurodegeneration and extends lifespan, revealing a gut-brain axis. Our studies demonstrates that ninaD is a central regulator of cholesterol homeostasis and a longevity-promoting factor.

neuroscience↗

bioRxiv2020

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

Small nucleolar RNAs (snoRNAs) are non-coding RNAs conserved from archeobacteria to mammals. In humans, various snoRNAs have been associated with pathologies as well as with cancer. Recently in Drosophila, a new snoRNA named jouvence has been involved in lifespan. Since snoRNAs are well conserved through evolution, both structurally and functionally, jouvence orthologue has been identified in human, allowing hypothesizing that jouvence could display a similar function (increasing healthy lifespan) in human. Here, we report the characterization of the human snoRNA-jouvence, which was not yet annotated in the genome. We show, both in stably cancerous cell lines and in primary cells, that its overexpression stimulates the cell proliferation. In contrast, its knockdown, by siRNA leads to an opposite phenotype, a decrease in cell proliferation. Transcriptomic analysis reveals that overexpression of jouvence leads to a dedifferentiation signature of the cells, a cellular effect comparable to rejuvenation. Inversely, the knockdown of jouvence leads to a decrease of genes involved in ribosomes biogenesis and spliceosome in agreement with the canonical role of a H/ACA box snoRNA. In this context, jouvence could represent a now tool to fight against the deleterious effect of aging, as well as a new target in cancer therapy.

genetics↗