Biology subjects

Pirrotta, M.

Publications and source records attributed to Pirrotta, M..

2 recordsLinked to original sources

bioRxiv2024

G-quadruplex formation in long non-coding RNAs dysregulated in colorectal cancer

Non-coding RNAs (ncRNAs) in human cells do not lead to protein synthesis and constitute a substantial portion of the transcriptome. Human long non-coding RNAs (lncRNAs) orchestrate critical cellular functions influencing development, differentiation, and metabolism. Dysregulation of lncRNAs has been correlated with several pathological conditions such as neurodegenerative and autoimmune disorders, diabetes, and cancer. Recent reports have suggested the involvement of G4s in lncRNAs to regulate colorectal cancer (CRC) carcinogenesis. In this study, we investigate the occurrence and distribution of G4s in the LINC01589, MELTF-AS1, and UXT-AS1 lncRNAs, which have been reported to be dysregulated in CRC. Using a combination of in silico tools and in vitro biophysical techniques, we show that these lncRNAs form stable, parallel, and intramolecular G4s. Furthermore, we establish the formation of G4s within these lncRNAs in CRC using cell-based assays, including RNA G4-Immuno-FISH and G4RP-RT-qPCR. This is the first systematic study of G4s in lncRNAs dysregulated in CRC, and our findings highlight the diagnostic and therapeutic potential of G4s in CRC.

biochemistry↗

bioRxiv2020

Disclosing the actual efficiency of G-quadruplex DNA-disrupting small molecules

The quest for small molecules that avidly bind to G-quadruplex-DNA (G4-DNA, or G4), so called G4-ligands, has invigorated the G4 research field from its very inception. Massive efforts have been invested to i- screen or design G4-ligands, ii- evaluate their G4-interacting properties in vitro through a series of now widely accepted and routinely implemented assays, and iii- use them as unique chemical biology tools to interrogate cellular networks that might involve G4s. In sharp contrast, only uncoordinated efforts at developing small molecules aimed at destabilizing G4s have been invested to date, even though it is now recognized that such molecular tools would have tremendous application to neurobiology as many genetic and age-related diseases are caused by an over-representation of G4s, itself caused by a deficiency of G4-resolving enzymes, the G4-helicases. Herein, we report on our double effort to i- develop a reliable in vitro assay to identify molecules able to destabilize G4s, the G4-unfold assay, and ii- fully characterize the first prototype of G4-disrupting small molecule, a phenylpyrrolcytosine (PhpC)-based G-clamp analog.

biophysics↗