Visualization of ligand-induced c-MYC duplex-quadruplex transition and direct exploration of the altered c-MYC DNA-protein interactions in cells.

Ligand-Induced duplex-quadruplex transition within the c-MYC promoter region is one of the most studied and advanced ideas for c-MYC regulation. Despite its importance, there is a lack of methods for monitoring such process in cells, hindering a better understanding of the essence of c-MYC G-quadruplex as a drug target. Here we developed a new fluorescent probe ISCH-MYC for specific c-MYC G-quadruplex recognition based on GTFH (G-quadruplex-Triggered Fluorogenic Hybridization) strategy. We validated that ISCH-MYC displayed distinct fluorescence enhancement upon binding to c-MYC G-quadruplex, which allowed the duplex-quadruplex transition detection of c-MYC G-rich DNA in cells. Using ISCH-MYC, we successfully characterized the induction of duplex to G-quadruplex transition in the presence of G-quadruplex stabilizing ligand PDS and further monitored and evaluated the altered interactions of relevant transcription factors Sp1 and CNBP with c-MYC G-rich DNA. Thus, our study provides a visualization strategy to explore the mechanism of G-quadruplex stabilizing ligand action on c-MYC G-rich DNA and relevant proteins, thereby empowering future drug discovery efforts targeting G-quadruplexes.

Visualization of NRAS RNA G-Quadruplex Structures in Cells with an Engineered Fluorogenic Hybridization Probe.

The RNA G-quadruplex is an important secondary structure formed by guanine-rich RNA sequences. However, its folding studies have mainly been studied in vitro. Accurate identification of RNA G-quadruplex formation within a sequence of interest remains difficult in cells. Herein, and based on the guanine-rich sequence in the 5'-UTR of NRAS mRNA, we designed and synthesized the first G-quadruplex-triggered fluorogenic hybridization (GTFH) probe, ISCH-nras1, for the unique visualization of the G-quadruplexes that form in this region. ISCH-nras1 is made up of two parts: The first is a fluorescent light-up moiety specific to G-quadruplex structures, and the second is a DNA molecule that can hybridize with a sequence that is adjacent to the guanine-rich sequence in the NRAS mRNA 5'-UTR. Further evaluation studies indicated that ISCH-nras1 could directly and precisely detect the targeted NRAS RNA G-quadruplex structures, both in vitro and in cells. Thus, this GTFH probe was a useful tool for directly investigating the folding of G-quadruplex structures within an RNA of interest and represents a new direction for the design of smart RNA G-quadruplex probes.

Valley Polarization and Valleyresistance in a Monolayer Transition Metal Dichalcogenide Superlattice.

A significant, fundamental challenge in the field of valleytronics is how to generate and regulate valley-polarized currents in practical ways. Here, we discover a new mechanism for producing valley polarization in a monolayer transition metal dichalcogenide superlattice, in which valley-resolved gaps are formed at the supercell Brillouin zone boundaries and centers due to intervalley scattering. When the incident energy of the electron lies in the gaps, the available states are valley polarized, thus providing a valley-polarized current from the superlattice. We show that the direction and strength of the valley polarization may be further tuned by varying the potential applied to the superlattice. The transmission can have a net valley polarization of 55% for a four-period heterostructure. Moreover, two such valley filters in series may function as an electrostatically controlled giant valleyresistance device, representing a zero-magnetic field counterpart to the familiar giant magnetoresistance device.