Auburn University Assistant Professor of Biological Sciences Joanna Sztuba-Solinska recently received a big boost in her quest to discover what makes viruses target specific enzymes within cells.
The accomplished researcher and her team received a $451,661 grant from the National Institutes of Health or NIH, that will propel her team’s research tasked with discovering the processes that regulate viral RNA — or ribonucleic acid, the molecule essential in coding, decoding, regulation and expression of cellular components — during an infection. Specifically, Sztuba-Solinska’s team is analyzing PAN RNA, a long non-coding RNA that is produced during the reactivation of Kaposi’s sarcoma-associated herpesvirus, or KSHV, which causes cancer.
PAN RNA is particularly of interest to Sztuba-Solinska and her team because it shares some structural and functional features with cellular long non-coding RNAs that are implicated in cancer development. PAN also is the most abundant transcript that accumulates in KSHV-induced tumors and must be carefully regulated.
Sztuba-Solinska hopes that exploration will result in greater knowledge about cellular processes that influence viral infectivity, which can be extrapolated to other viruses, including SARS CoV-2 — the virus that causes COVID-19.
“We are currently using the CRISPR/CAS system and editing two human genes that we suspect are responsible for PAN RNA regulation to see what happens with the virus,” Sztuba-Solinska said. “Viruses decorate their RNAs with chemical groups so they are not recognized by the cell as a danger. It is a sort of camouflaging strategy they use, and all viruses do that, no matter if we’re talking about coronaviruses, herpes viruses or any other viruses we study. It’s a universal mechanism.
“Those decorations were discovered a long time ago, but we didn’t have the tools to study that back then. This grant will allow us to study the most abundant chemical modification that has been discovered in viral RNAs, which is called pseudouridine.”
The NIH Research Enhancement Award will fund Sztuba-Solinska’s study titled “Fifth Nucleotide and Its Potential to Modulate Long Non-Coding RNA Structure.”
“This is a great achievement for my team,” said Sztuba-Solinska, who plans for her team to soon publish findings from this study in high-impact factor research journals as it progresses. “It will let us continue on with what we’re doing the next three years. It also will allow graduate and undergraduate students in my lab to be involved in cutting-edge analyses experiencing the excitement that comes from discovering the answers to important biological questions.”
If Sztuba-Solinska and her team can identify the cellular mechanisms that regulate viral infectivity, that could help other researchers and health care professionals treat viral diseases down the road.
“We want to identify the cellular machinery that is exploited by KSHV to hide PAN RNA from the cellular immune surveillance,” she said. “When we identify them, we will be able to define what happens to PAN RNA if we get rid of these enzymes. How would that affect that RNA, and how would that affect the virus replication and pathogenicity?
“Studying that mechanism can lead to the discovery of some weak points in the viral infectivity cycle, and after that, all there is is therapy or antiviral development to basically trigger that weakness.”
Determining specifics regarding triggers and vulnerabilities within a cell’s structure can go a long way to actual treatment of viruses.
“If you identify a specific modification within the RNA and you know how that modification affects RNA structure and function, you can target that particular modified RNA element with drugs,” Sztuba-Solinska said. “The drug can alter the RNA biology, leading to the disruption of viral infectivity cycle, and that’s the route we want to take for the effective development of treatment.”
What makes Sztuba-Solinska’s research even more appealing to the research and medical world, she says, is its potential to be applied to all types of viruses, including the coronavirus.
“It’s basic research, so the findings might be much more broadly applicable to other viral systems,” said Sztuba-Solinska, whose team also continues to study the coronavirus using CytoViva microscopes. “This is a good model system, because whatever we find there might also be applicable to other viruses.”