Biology subjects

Valenti, P.

Publications and source records attributed to Valenti, P..

3 recordsLinked to original sources

bioRxiv2025

3D dynamics of trans enhancer-promoter interactions in living Drosophila embryos reveals spatiotemporal thresholds for transcription activation

While it is well acknowledged that specific enhancer-promoter interactions are essential for transcription, the spatiotemporal thresholds required for transcription initiation remain unclear. Here, we employed the phenomenon of transvection, where an enhancer activates the target gene in trans at the homologous position, to analyze the mechanism of long-range enhancer-promoter interactions. We combined the MS2- and PP7-based RNA labeling with the ParB/parS DNA labeling to simultaneously visualize active transcription and a target DNA locus in living Drosophila embryos. By quantifying the 3D enhancer-promoter distances in nuclei that exhibited active or inactive transcription, we found that sustained proximity between the enhancer and promoter is necessary and sufficient to initiate transcription. The enhancer-promoter proximity was established before transcription initiation and remained stable after the termination, suggesting the localization of an enhancer and the target promoters in a "transcription hub." When transvection occurred, the cis-linked reporter gene showed a delayed activation and reduced mRNA production, suggesting homologous promoter competition in the hub. Our DNA-labeled co-transvection assay sheds insights into the activation criteria for the long-range enhancer-promoter interactions and provides a stepping stone for future endeavors to understand the complex gene regulation in 3D space.

developmental biology↗

bioRxiv2021

Drosophila primary microRNA-8 encodes a microRNA encoded peptide (miPEP) acting in parallel of miR-8

BackgroundRecent genome-wide studies of many species reveal the existence of a myriad of RNAs differing in size, coding potential and function. Among these are the long non-coding RNAs, some of them producing functional small peptides via the translation of short ORFs. It now appears that any kind of RNA presumably has a potential to encode small peptides. Accordingly, our team recently discovered that plant primary transcripts of microRNAs (pri-miRNAs) produce small regulatory peptides (miPEPs) involved in auto-regulatory feedback loops enhancing their cognate microRNA expression which in turn controls plant development. Here we investigate whether this regulatory feedback loop is present in Drosophila melanogaster. ResultsWe perform a survey of ribosome profiling data and reveal that many pri-miRNAs exhibit ribosome translation marks. Focusing on miR-8, we show that pri-miR-8 can produce a miPEP-8. Functional assays performed in Drosophila reveal that miPEP-8 affects development when overexpressed or knocked down. Combining genetic and molecular approaches as well as genome-wide transcriptomic analyses, we show that miR-8 expression is independent of miPEP-8 activity and that miPEP-8 acts in parallel to miR-8 to regulate the expression of hundreds of genes. ConclusionTaken together, these results reveal that several Drosophila pri-miRNAs exhibit translation potential. Contrasting with the mechanism described in plants, these data shed light on the function of yet un-described pri-microRNA encoded peptides in Drosophila and their regulatory potential on genome expression.

developmental biology↗

bioRxiv2020

Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: in vivo, in silico and in vitro preliminary evidences

Lactoferrin, a multifunctional cationic glycoprotein, secreted by exocrine glands and neutrophils, possesses an antiviral activity extendable to SARS-CoV-2. We performed in vitro assays proving lactoferrin antiviral activity through direct attachment to both virus and cell surface components. This activity varied according to concentration (100/500g/ml), multiplicity of infection (0.1/0.01) and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between the lactoferrin and the Spike S glycoprotein, thus hindering the viral entry into the cells. Hence, we conducted a clinical trial to investigate effect and tolerability of a liposomal lactoferrin formulation as a supplementary nutraceutical agent in mild-to-moderate and asymptomatic COVID-19 patients. A total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided in 3 groups according to the administered regimen. Thirty-two patients, 14 hospitalised and 18 in home-based insolation received oral and intranasal liposomal bovine lactoferrin (bLf), 32 hospitalised patients were treated with standard of care treatment (hydroxychloroquine, azitromicin and lopinavir/darunavir), and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, not-treated, healthy subjects were added as a control group for ancillary analysis. bLf-supplemented COVID-19 patients obtained an earlier and significant (p < 0,0001.) median rRT-PCR SARS-COV-2 RNA negative conversion than standard of care-treated and non-treated COVID-19 patients (14.25 vs 27.13 vs 32.61 days, respectively). In addition, bLf-supplemented COVID-19 patients showed significant fast clinical symptoms recovery than standard of care-treated and non-treated COVID-19 patients. Moreover, in bLf-supplemented patients, a significant decrease of either serum ferritin or IL-6 levels or host iron overload, all parameters characterizing inflammatory processes, were observed. Serum D-dimers was also found significantly decreased following bLf supplement. No adverse events were reported. These in vitro and in vivo observations led us to speculate a potential and safe supplementary role of Blf in the management of mild-to-moderate and asymptomatic COVID-19 patients.

microbiology↗