Researchers at the University of Cambridge have developed a new way to detect chemical modifications in RNA as it is being made. The researchers used tiny pores and special DNA:RNA nanostructures to sense whether certain modified building blocks were added to RNA during transcription. This advancement makes it easier to analyze even short strands of RNA, which are usually difficult to study.

To show how their method works, the researchers tested it on two kinds of modified RNA. For short RNA molecules, they added a biotin-tagged version of uridine, one of RNA’s basic components. They then used a nanopore setup to detect this tag. For longer RNA molecules, they used a version of uridine with an azide group, which can be chemically linked to DNA probes through a process called click chemistry. This made it possible to measure how much modified uridine had been incorporated.

Their new platform allows scientists to study RNA modifications at the single-molecule level using solid-state nanopores. This can help researchers better understand how RNA is made and modified, which is essential for learning how cells respond to different conditions or how diseases develop.