Unipd research: DNA paves the way for new therapeutic targets

09.08.2023

Published as a breakthrough article in Nucleic Acids Research, the study entitled Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells demonstrates that i-motifs (iMs) and G-quadruplexes (G4s) are not only present in live human cells, therefore in non-acidic conditions, they also perform a control function in the expression of cellular genes. These original findings are the results of the work performed by a research team led by Prof Sara Richter of the University of Padua.

As demonstrated by Watson and Crick in 1953, the genetic information of every cell is contained in DNA that forms the double helix structure. Over the years, numerous studies have proved that the structure of DNA is much more dynamic than initially thought. Alternative constructs to the double helix, defined as non-canonical structures, must be assumed. Among these, i-motifs (iMs) and G-quadruplexes (G4s) are four-stranded structures that can form in particular regions of DNA based on their composition. G-quadruplexes (G4s) and i-motifs (iMs) are non-canonical nucleic acid structures, an alternative to the Watson-Crick double-helix conformation.

To date, G4s are characterized much more than iMs are, as it was long believed that they could not be present in cells because their formation only occurred in acidic conditions and test tubes.

First authors of the study Irene Zanin and Emanuela Ruggiero, from the Department of Molecular Medicine of the University of Padua explain, “Our work highlights how the presence of iMs and G4s hold an intrinsic feature of each cell line and therefore how these structures control important cellular functions. Given the involvement in key roles of cell biology, iMs, and G4s represent new therapeutic targets for different and relevant human pathologies, such as cancer, infectious and neurodegenerative diseases.”