Understanding ribonucleic acid (RNA) and its chemical properties and biological mechanisms is a key area of focus in health research. RNA is critical in the processing and movement of genetic information and gene expression.
The way RNA folds into various tertiary structures determines its biological function, and being able to dissect and alter that process could lead to prevention of a multitude of retrovirus-induced diseases, including certain types of cancer. An interdisciplinary team of Mizzou researchers is one step closer to that goal.
Professor of Bioengineering and the Dalton Cardiovascular Research Center Li-Qun (Andrew) Gu and Shi-Jie Chen, joint Professor of Physics, Biochemistry and the MU Informatics Institute and their team recently published “Nanopore electric snapshots of an RNA tertiary folding pathway,” in the prestigious journal Nature Communications.
The paper outlines how the team used nanopore snapshots to determine RNA structures at various phases of the folding process and based on the nanopore signal, used computer simulations to understand important points that allow researchers to eventually derive the entire folding pathway and predict how a given strand of RNA will fold.
“Once they go through this nanopore, molecules can generate different signals,” Gu said. “Different domains of this RNA will generate quite different signals. From this current signal, you can discriminate which domain it is, and then we have a clue that the molecule may fold in a particular way.”
Being able to map the folding pathway of RNA has the potential to allow researchers to predict which molecules may fold in such a way that will cause adverse health effects. The specific RNA investigated by the team begins in an unfolded state before moving to an intermediate state, then into a pseudoknot structure — a compact bundling that approximates a knot but untangles when stretched out rather than tightening.
Understanding this process has the potential to allow pharmaceutical experts to design drugs that can intercept RNA at the intermediate stage, keeping it from folding into a potentially harmful structure, or even alter it in a way that allows the molecule to fold into a non-harmful structure.
“In order to go to the final structure, you have to unfold the misfolded structure first,” Chen said. “This can potentially tell us how to sabotage the folding of this molecule.”
Many of the students working alongside Gu and Chen on this groundbreaking research came to Mizzou as part of MU Engineering’s 2+2 and 3+2 programs. Students in these programs come from partner universities abroad, where they study for the first two or three years, then come to Mizzou to finish their degrees. The 2+2 program culminates in a bachelor’s degree, while 3+2 culminates in a master’s.
The opportunity to work on projects such as this and earn high-ranking journal credits are a key recruiting tool for potential undergraduates and graduate students alike. The researchers get much needed assistance, while students earn the opportunity to build up their resumes for future employment with a co-author credit in a major journal — a big feather in the cap for both undergraduate and graduate students.
“We set a goal,” said Dave Grant, Mizzou Engineering Career and Recruitment Coordinator. “When I meet with these students, we set a goal for them, and I talk to Andrew, too. … Andrew has been really good at saying, ‘If you come to my lab, we will publish.’”