Viral RNA undergoes conformational changes to hijack host cells, says study

Scientists from the University of Colorado Anschutz Medical Campus recently identified how an RNA molecule from a virus develops a complex, three-dimensional structure, and is capable of changing its shape to hijack host proteins. The particulars of this mechanism, distant to researchers for many years was demonstrated using cryogenic electron microscopy (cryo-EM).

Viral RNA undergoes conformational changes to hijack host cells, says study
Image Credit: University of Colorado Anschutz Medical Campus.

The observations demonstrate the occurrence of this molecular mimicry and shape-shifting. It also underlines the emerging power of cryo-EM to enable scientists a better means to examine multifunctional dynamic RNA structures that are vital in virology and biology. The observations are published in the Science journal.

Previously, we knew some basics about viral mimicry of tRNAs, but this example was a decade-old mystery. What we observed surprised us. Before advances in cryo-EM, visualizing this process was incredibly difficult or impossible. With cryo-EM, we observed for the first time the three-dimensional shape of this viral RNA, its motions, and how it binds to a cellular protein.”

Jeffrey Kieft PhD, Study Co-Author and Professor, University of Colorado School of Medicine

RNA molecules form complex 3-D shapes that dictate molecular function. Certain viral RNAs imitate the shape of tRNA—an important kind of RNA that delivers amino acids to the ribosome at the time of protein synthesis—a part of the overall scheme to hijack host cells. An “L” shape is formed by tRNA molecules in the cell.

We visualized the structure of the viral RNA molecule, expecting to see the classic ‘L’ shape. Instead, it forms a very different shape and interacts with cellular proteins in an unexpected way that involves changes in shape. Determining why this happens is the next step.”

Steve Bonilla PhD, Study Co-Author and HHMI Hanna H. Gray Post-Doctoral Research Fellow, University of Colorado School of Medicine

Along with observing the process for the first time, the scientists remark that this research highlights the role cryo-EM could perform in making similar discoveries. Cryo-EM employs electrons to see minuscule samples. The current research demonstrates how it enables a scientist to analyze elusive structures of small and dynamic RNAs that play vital roles in health and disease.

With the growing use of RNA-based therapeutics, three-dimensional RNA structures could be an important part of developing new examples. Therapeutics of the future might use RNA structure in rational ways. Studies like this help pave the way for exploring and thinking about this possibility.”

Steve Bonilla PhD, Study Co-Author and HHMI Hanna H. Gray Post-Doctoral Research Fellow, University of Colorado School of Medicine

Source:
Journal reference:

Bonilla, S. L., et al. (2021) A viral RNA hijacks host machinery using dynamic conformational changes of a tRNA-like structure. Science. doi.org/10.1126/science.abe8526.

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