Biology subjects

Parent, R.

Publications and source records attributed to Parent, R..

3 recordsLinked to original sources

bioRxiv2025

DDX5 and DDX17 RNA helicases regulate hepatitis B virus RNA splicing

Chronic HBV infection remains a major health burden worldwide and is the main driver of severe liver diseases. Liver pathogenesis is associated with the increased proportion of HBV spliced variants that encode viral proteins involved in liver disease progression. However, how HBV RNA splicing is regulated is poorly understood. Here, we focused on DDX5 and DDX17 RNA helicases, known to regulate HBV RNA metabolism and alternative splicing of host genes. By performing 5RACE-PCR combined with single molecule sequencing, we demonstrated that silencing both proteins increased the usage of a specific splicing donor site and the expression of the derived HBV spliced variants. Polysome fractionation highlighted the ability of these RNA species to encode new viral proteins potentially contributing to liver pathogenesis. Overall, our data established DDX5 and DDX17 helicases as master regulators of HBV RNA metabolism, by fine-tuning viral splicing, which is linked to HBV-induced liver pathogenesis and disease progression.

molecular biology↗

bioRxiv2022

Hepatocellular carcinoma hosts immature neurons and cholinergic tumors that correlate with adverse molecular features and outcomes

Background & aimsThe unexplained interpatient variation in hepatocellular carcinoma (HCC) remains a major challenge. We aimed at addressing the under-explored association between the disease and the hepatic autonomic nervous system (ANS). Methods & ResultsWe in-depth characterized the innervation of French biobanks HCC samples by conventional biochemistry methods. We also applied bioinformatics approaches to the TCGA dataset in order to stratify samples according to neural features and molecular correlates. We highlighted the predominant parasympathetic polarity of HCC nerves, and demonstrated that a cirrhotic rat model of aggressive HCC hosts liver neurogenesis with cholinergic features. Using the TCGA dataset, we then defined an HCC neural signature, derived from adrenergic and cholinergic receptor levels, that allowed patient stratification into two classes. Cholinergic tumors correlated with TP53 mutations (p [≤] 0.05), shorter progression-free interval (PFI) and overall survival (OS), displayed more pathogenic molecular traits (e.g., AFP-rich, proliferative tumors, mitotic functions including DNA repair, EMT, Ras, and Akt/mTOR pathways), aggressive HCC signatures and B cell accumulation. Instead, adrenergic tumors, predominant in patients aged >60 and with mutated CTNNB1, were correlated with better OS and PFI (p < 0.05), and numerous immune pathways. ConclusionsOur results depict neural features of HCC and how the existing tumor classification may also be shaped by neural inputs. Altogether, we show that the parasympathetic branch of the ANS is implicated in the pathobiology of HCC, and advocate for the use of ANS-targeting drugs in HCC research, many of which are clinically safe and well characterized.

cancer biology↗

bioRxiv2020

Carbamazepine and GABA have distinct effects on seizure onset dynamics in mouse brain slices

Optimizing antiepileptic drug therapy is very challenging due to the absence of a reliable method to assess how brain activity changes between seizures. This work uses the Taxonomy of Seizure Dynamics (Saggio et al., 2020) to investigate how anticonvulsants influence seizure onset dynamotypes. The no Mg2+ /high K+ mouse brain-slice seizure model (N = 92) was used to generate consistent epileptiform onsets. We compared the onset bifurcations of controls with slices treated with either GABA or carbamazepine. Each anticonvulsant uniquely changed the types of bifurcations in the slices. This experiment provides proof-of-concept evidence that brain states exist on a "map" of seizure dynamics, and that antiepileptic drugs with different mechanisms can change the positioning of the brain states on the map. Impact statementAntiepileptic drugs modify underlying brain states and influence the pathway into seizure onset in brain slices.

bioinformatics↗