Exploring Z-RNA’s Role in Immune Response

Quentin Vicens, an Assistant Professor of Biology and Biochemistry at the University of Houston, has been granted $1.2 million by the National Institute of General Medical Sciences to investigate the enigmatic Z-RNA structure found within human cells. This structure plays a pivotal role in immune response.

This collaborative effort involves the laboratory of Beat Vögeli, an Associate Professor at the University of Colorado, who is also a co-recipient of the award.

Together, Vicens, Vögeli, and their respective research teams are dedicated to unraveling the mysteries surrounding Z-RNA. They aim to decipher the mechanisms behind Z-RNA formation, its prevalence in genetic material, and its implications for proteins known to interact with this structure.

Their primary focus centers on RNA editing, a process where a single RNA letter is transformed into another, akin to changing a letter in a word to create a new word.

This editing process is more prevalent in conditions such as cancer and infections and is closely linked to the presence of a unique protein component that can bind to Z-RNA.

Helices come in generally two ‘flavors.’ The typical formation is to the right. The one to the left is not stable, but it does occur in cells. Yet researchers do not yet truly understand how it is possible for this helix to occur in cells when it is not stable.

Quentin Vicens, Faculty Member, College of Natural Sciences and Mathematics., University of Houston

Vicens added, “We want to know what happens at the molecular level that causes this RNA structure to flip from one direction to another and then revert. Think of a staircase spiraling up to the right that one day spirals to the left.”

The team will employ nuclear magnetic resonance (NMR) techniques, an area of expertise in Vögeli’s laboratory. NMR involves the use of magnets and radio waves to capture images of the minute structures within our cells, allowing them to observe the transformation of RNA from its typical form to the Z-form.

Meanwhile, Vicens' research group is exploring cryo-electron microscopy, enabling them to visualize large assemblages of proteins and molecules in a frozen, glassy state. They are also venturing into the realm of genomics by investigating how natural modifications to cellular RNA influence the adoption of Z-RNA within cells.

While this research delves deep into the fundamental science of RNA biology, it holds the potential to advance our understanding of and potentially address various diseases, including Aicardi-Goutières syndrome, cancer, and autoimmune deficiencies.

When RNA gets edited incorrectly, it can lead to these diseases, making it vital that we fully understand their function. We hope that this work reveals how proteins and Z-RNA work together, potentially giving us new ways to diagnose or treat these illnesses.

Quentin Vicens, Faculty Member, College of Natural Sciences and Mathematics, University of Houston