Scientists led by Dr. Chen Gang from the Chinese University of Hong Kong (Shenzhen) have launched a new method to identify and interact with specific RNA structures. Their research features Cell Reports Physical Sciencesexplains how specially designed molecules called dual-affinity peptide nucleic acids attach to both double-stranded RNA regions (the portions of RNA where the two strands pair together) and single-stranded RNA regions (where the RNA remains unpaired), Junction.
RNA is an important molecule in living organisms, helping to perform a variety of functions, including regulating genes and producing proteins. Its complex folded shape, called secondary structure, makes it difficult to target specific areas. Previous approaches, such as synthetic molecules called antisense oligonucleotides, which bind to specific RNA sequences to block their function, and similar compounds, only worked on single-stranded or loosely paired double-stranded RNA regions, while Leaving many other important structures out of reach. Dual-affinity peptide nucleic acids overcome this limitation by combining two types of targeting mechanisms. One type is designed for flexible single-stranded RNA, while the other type is used to connect rigid double-stranded regions. They can bind tightly to the region where these two regions meet, providing new ways to study and manipulate RNA.
Experts tested the molecules on different types of RNA, such as hairpin RNA, which forms a ring-like structure, precursor microRNA, the immature form of microRNA before it becomes active, and messenger RNA, a type of RNA that carries genetic instructions. molecule) protein. Experiments have proven their versatility. For example, they demonstrated that specific dual-affinity peptide nucleic acids can block the activity of the Dicer enzyme, which cleaves precursor microRNA into its mature form. This ability could open the door to regulating microRNA levels in cells. In another experiment, the molecules increased the efficiency of the ribosomal frameshift process, a mechanism used by some viruses, including SARS-CoV-2 and HIV-1, to change the reading frame of genes to produce essential proteins. By targeting structured regions in messenger RNA, the researchers highlight the potential applications of this innovative technology.
“By combining two types of synthetic molecules, we achieved new levels of precision and programmability in targeting RNA structures,” explained Dr. Chen, highlighting how this platform could lead to new ways of treating disease or studying RNA in detail. tool.
Notably, the study also explored how these molecules target RNA structures associated with certain diseases. For example, neurodegenerative diseases are often caused by faulty RNA splicing, in which RNA segments join together incorrectly. These dual-affinity peptide nucleic acids can potentially correct such errors by focusing on specific structural regions, much like molecular tools that repair or probe important RNA conformations.
RNA-targeted treatments and research have made great strides in recent years. This research represents an important step forward, providing more accurate and adaptable tools for RNA work. These discoveries pave the way for applications in disease treatment and scientific exploration, and have broad prospects in the future.
Journal reference
Lu Rui, Deng Li, Lian Yu, etc. “Identification of RNA secondary structure using a programmable peptide nucleic acid-based platform.” Cell Reports Physical SciencesMay 2024 102150.
About the author
Dr. Chen Gang Associate Professor, School of Medicine, The Chinese University of Hong Kong (Shenzhen) (Graduated from the Department of Chemistry, University of Science and Technology of China in 2001 with a bachelor’s degree. Professor Douglas TURNER’s doctoral work from the Department of Chemistry, University of Rochester, involved thermodynamics and nuclear magnetic resonance research on the internal loops of RNA. A better understanding of the thermodynamic sequence dependence of RNA structure will improve the accuracy of RNA research in the TINOCO laboratory using laser optical tweezers to mechanically unfold and fold RNA pseudoknots, which are the ribosomes of cis-acting mRNA structures. Reading frame regulation provides new insights. He is a research associate in the laboratory of Professor David MILLAR in the Department of Molecular Biology at Scripps Research, working on the assembly of HIV-1 Rev-RRE using single-molecule fluorescence techniques 2010-7. In September, he joined the Department of Chemistry and Biochemistry of Nanyang Technological University in Singapore as a teacher. In 2020, he joined the Chinese University of Hong Kong (Shenzhen).
