Image: An ancient bacterial enzyme (grey) crawls along a tangled strand of RNA (orange), creating a complimentary strand of DNA (blue). This enzyme, called GsI-IIC RT, and part of a group of enzymes known as TGIRTs, have novel properties that make it easier to detect RNA biomarkers from cancer and other disorders (Photo courtesy of the University of Texas at Austin).
A new tool has been developed for liquid biopsy that can detect RNA biomarkers from cancer cells in a patient's blood much more accurately and completely than other existing methods. This could soon provide doctors with a more complete picture of an individual's disease.
Many current liquid biopsies can detect DNA in blood; others can detect RNA, although they tend to miss many key RNA biomarkers and misinterpret others. An ancient enzyme detects the full range of RNAs with much higher accuracy, which is helpful for understanding both the general profile of a disease such as cancer and specific information about its activity in a particular patient.
Scientists at the University of Texas at Austin (TX, USA) uncovered for the first time the molecular structure of this RNA-detecting enzyme in action, offering clues about how it works and how it can be improved for use in medical tests. Both DNA and RNA bear genetic information useful for understanding a disease state such as cancer. Bacterial group II intron reverse transcriptases (RTs) function in both intron mobility and RNA splicing and are evolutionary predecessors of retrotransposon, telomerase, and retroviral RTs as well as the spliceosomal protein Prp8 in eukaryotes. The team determined a crystal structure of a full-length thermostable group II intron RT in complex with an RNA template-DNA primer duplex and incoming deoxynucleotide triphosphate (dNTP).
Thermostable Group II Intron Reverse Transcriptases (TGIRTs) are ancient enzymes that date to a time when genetic information was stored mainly in RNA, but life was transitioning to DNA. Another major finding of the study was that TGIRT enzymes are remarkably similar to enzymes from RNA viruses, which copy RNA. This highlights the potential evolutionary role of TGIRTs and other closely related enzymes in the evolution of present-day organisms, which use DNA for genetic material.
Alan M. Lambowitz, PhD. a professor of Cellular and Molecular Biology and lead investigator, said, “DNA biomarkers are static. They provide information about mutations that cause a disease, but they don't provide information about the effect of these mutations on cellular processes, which can differ in different individuals. Monitoring cellular RNAs provides a snapshot of exactly what is happening in diseased tissue, such as a tumor, at a particular time. The method can be used to monitor day-to-day progression of the disease and response to treatment and to predict how different individuals with the same cancer will respond to different treatments.” The study was published on November 16, 2017, in the journal Molecular Cell.
University of Texas at Austin