Biology subjects

D'Onghia, M.

Publications and source records attributed to D'Onghia, M..

3 recordsLinked to original sources

bioRxiv2025

Endogenous retrotransposon reverse transcriptase supports osteocyte function: implications for antiretroviral therapy-associated bone loss

Retrotansposable elements such as LINE-1 and HERV-K encode endogenous reverse transcriptases (RTs) with emerging roles in human biology. People living with HIV, particularly those receiving nucleoside reverse transcriptase inhibitor (NRTI)-based therapy, have increased risk of low bone mineral density (BMD), but the underlying mechanisms remain unclear. Here we show that endogenous RT activity, estimated by L1-Ta and HERV-K DNA content, is enriched in human bone and markedly reduced in osteoporosis, where it correlates with BMD and osteocyte gene expression. In vitro, nucleoside reverse transcriptase inhibitors (NRTIs), widely used as antiretroviral drugs, impair osteocyte endocrine function, disrupting vitamin D3-induced FGF23 production and parathyroid hormone- mediated regulation of SOST. These findings identify endogenous RT activity as a regulator of osteocyte function and bone homeostasis, and suggest that its pharmacological inhibition may contribute to antiretroviral therapy-associated bone loss.

molecular biology↗

bioRxiv2025

Histone Succinylation-Driven LINE-1 Reactivation Links High-Fat Diet Stress to Hepatic Inflammation and Liver Disease

Endogenous retroelements such as LINE-1 (L1) are stress-responsive genomic elements increasingly implicated in stress induced inflammation and associated pathogenic states. Here, we uncover a novel mechanism whereby high-fat diet-associated palmitic acid stress triggers chromatin remodeling that derepresses L1 elements and an IRF3-dependent interferon response, leading to innate immune activation in hepatocytes. Mechanistically, we show that that palmitic acid exposure promoted p300/CBP-mediated H3K122 succinylation at L1 promoters, coupled with reduced sirtuin desuccinylase cofactor availability, thereby enhancing chromatin accessibility and transcription. Antisense oligonucleotide-mediated L1 silencing abrogated this response by resetting chromatin homeostasis, demonstrating a causal role for L1 in palmitate-induced inflammation. In vivo, L1 knockdown in a fructose-palmitate-cholesterol (FPC) diet-induced mouse model of MASLD/MASH improved insulin sensitivity, reduced hepatic inflammation, and ameliorated fibrosis. These findings identify L1 derepression as a key epigenetic and inflammatory effector of dietary lipid stress and establish L1 inhibition as a potential therapeutic strategy for metabolic liver disease.

molecular biology↗

bioRxiv2022

Discovering host protein interactions specific for SARS-CoV-2 RNA genome

SARS-CoV-2, a positive single-stranded RNA virus, interacts with host cell proteins throughout its life cycle. These interactions are necessary for the host to recognize and hinder the replication of SARS-CoV-2. For the virus, to translate, transcribe and replicate its genetic material. However, many details of these interactions are still missing. We focused on the proteins binding to the highly structured 5 and 3 end regions of SARS-CoV-2 RNA that were predicted by the catRAPID algorithm to attract numerous proteins, exploiting RNA-Protein Interaction Detection coupled with Mass Spectrometry (RaPID-MS) technology. The validated interactors, which agreed with our predictions, include pseudouridine synthase PUS7 that binds to both ends of the viral RNA. Nanopore direct-RNA sequencing confirmed that the RNA virus is heavily modified, and PUS7 consensus regions were found in both SARS-CoV-2 RNA end regions. Notably, a modified site was detected in the viral Transcription Regulatory Sequence - Leader (TRS-L) and can influence the viral RNA structure and interaction propensity. Overall, our data map host protein interactions within SARS-CoV-2 UTR regions, pinpointing to a potential role of pseudouridine synthases and post-transcriptional modifications in the viral life cycle. These findings contribute to understanding virus-host dynamics and may guide the development of targeted therapies.

molecular biology↗