RNA is a heavily studied category of biological molecules that serve a diverse set of roles within every cell. Though scientists are beginning to understand the function of many RNAs, it remains a mystery how RNAs can fold into shapes and structures to carry out these functions. Breakthroughs in simulation software allow scientists to peak into the fast-moving molecular world to hypothesize how this folding may occur. Recent collaborative efforts between researchers at Northwestern University, the University of Albany, and the Ohio State University led to beautiful, data-driven movies of RNA molecules twisting and folding in real time.

Scientists understand that RNA starts as a basic, unfolded structure (point A) which eventually becomes a more complicated, folded RNA structure (point B). However, it is unknown how the RNA changes from point A to point B. To better understand the process of RNA folding, this team presents a new method called “Reconstructing RNA Dynamics from Data,” or R2D2. At its heart, this is a powerful simulation that relies on experimental data. First, the individual nucleic acid units of the RNA must be determined by nucleotide sequencing. Then, by combining the nucleotide sequence data with advanced simulations and predicted lengths between individual atoms, the model guesses the most likely shapes and structures adopted by the RNA. Finally, the structures serve as the starting point for further simulations that show the wiggles and twists of the RNA in detail.

In this study, the research team notes that they modeled a small, simple RNA molecule. From these simulations, they concluded that even simple RNA molecules undergo many changes in shape and structure throughout their lifetime. This is a major step toward understanding the many motions of RNA in your cells. Finally, we may begin to develop a deep understanding of RNA and its functions through the way it moves. Scientists hope to use R2D2 to model more complicated RNA molecules in greater detail.

This study was led by researchers Angela Yu, Luyi Cheng, and Dr. Julius Lucks from the Department of Chemical and Biological Engineering at Northwestern University; Paul Gaspar, Simi Kaur, and Dr. Alan Chen from the Department of Chemistry at the University of Albany; and Lien Lai and Dr. Venkat Gopalan from the Department of Chemistry and Biochemistry at The Ohio State University.

Managing Correspondent: Koby Ljunggren

Press Articles: Ground-breaking films show RNA’s complex curves take shape. Nature Research Highlights.

RNA ties itself in knots, then unties itself in mesmerizing video. Live Science.

Original Article: Computationally reconstructing cotranscriptional RNA folding from experimental data reveals rearrangement of non-native folding intermediates. Molecular Cell.

Image Credit: Pixabay