Biology subjects

Bernoud-Hubac, N.

Publications and source records attributed to Bernoud-Hubac, N..

3 recordsLinked to original sources

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↗

bioRxiv2018

Expression of fatty acid transport protein in retinal pigment cells promotes lipid droplet expansion and photoreceptor homeostasis

Increasing evidence suggests that dysregulation of lipid metabolism is associated with neurodegeneration in retinal diseases such as age-related macular degeneration and in brain disorders such as Alzheimers and Parkinsons diseases. Lipid storage organelles (lipid droplets, LDs), accumulate in many cell types in response to stress, and it is now clear that LDs function not only as lipid stores but also as dynamic regulators of the stress response. However, whether these LD functions are always protective or can also be deleterious to the cell is unknown. Here, we investigated the consequences of LD accumulation on retinal cell homeostasis in transgenic flies and mice overexpressing fatty acid transport protein (FATP) in retinal pigment cells (RPCs). In wild-type Drosophila, overexpression of dFatp specifically in RPCs resulted in an expansion of LD size in both RPCs and in neighboring photoreceptors but was non-toxic. Similarly, in mice, LD accumulation induced by RPC-specific expression of human FATP1 was non-toxic and promoted mitochondrial energy metabolism in both RPCs and photoreceptor cells. In contrast, RPC-specific dFatp knockdown reduced neurodegeneration in Aats-metFB Drosophila mutants, which carry a defective respiratory chain, indicating that abnormal LD accumulation can be toxic under pathological conditions. Collectively, these findings indicate that FATP-mediated LD formation in RPCs induces a non-autonomous increase of LDs in photoreceptors that promotes homeostasis under physiological conditions but can be deleterious under pathological conditions.\n\nAuthor SummaryLipids are major cell constituents and are present in the membranes, as free lipids in the cytoplasm, or stored in vesicles called lipid droplets (LDs). Under conditions of stress, lipids stored in LDs can be released to serve as substrates for energy metabolism by mitochondria. However, lipid storage is deregulated in many degenerative disorders such as age-related macular degeneration and Alzheimers disease. Thus, it is unclear whether accumulation of LDs is protective or can also be toxic. To address this question, we examined the consequences of enforced LD accumulation on the health of retinal cells in flies and mice. Like humans, fly and mouse retinas contain retinal pigment cells (RPC) that support the functions of neighboring photoreceptor cells. We found that overexpression of the fatty acid transport protein (FATP) in RPCs induced accumulation of LDs in both transgenic flies and mice. Moreover, LD accumulation in RPCs had a beneficial effect on juxtaposed photoreceptors under normal physiological conditions, but was toxic under pathological stress conditions. We propose that lipid storage is a mechanism of cellular communication that is essential to maintain photoreceptor health.

cell biology↗