This project explores the mechanical and structural behavior of DNA–RNA hybrids and long noncoding RNAs (lncRNAs) through multidisciplinary biophysical approaches. We will follow three lines of research. First, we will focus on the mechanics of DNA-RNA hybrids using magnetic and optical tweezers to perform force-extension measurement on single-stranded RNA (RNA) and ssRNA complexed with complementary ssRNA or ssDNA molecules. Atomic force microscopy (AFM) will also be used to analyze hybrid structures and dynamics both in air and liquid environments. Second, we will investigate two lncRNAs—NIHCOLE and CONCR—involved in DNA repair and chromatid cohesion, respectively. Their structures and protein interactions (with Ku70/Ku80 and DDX11) will be studied using nanopore techniques and the OT-Curtains single-molecule assay, allowing real-time observation of RNA–protein binding and structural changes. The third research line will employ super-resolution microscopy to visualize the spatial organization of these lncRNAs. By labeling specific RNA regions or immobilizing them on DNA origami scaffolds, this research line aims to correlate RNA folding, Mg²⁺-induced tertiary structures, and protein interactions, combining advanced microscopy and molecular manipulation methods.