Researchers at Roswell Park Cancer Institute (RPCI) have made new findings about the causes and impacts of RNA modification or "editing." Innate immune cells - the body's first line of defense - possess the ability to extensively change genetic information by means of RNA modification as a response to factors associated with inflammation. Further, aberrations in this process may predispose humans and other mammals to viral infections, cancer or other chronic diseases, according to the study, which was published in Nature Communications.
A team led by Bora Baysal, MD, PhD, Associate Professor in the Department of Pathology & Laboratory Medicine, in collaboration with the research group of Santosh Patnaik, MD, PhD, Assistant Professor in the Department of Thoracic Surgery, determined that inflammatory factors such as hypoxia, or a low-oxygen environment, and interferons, cellular proteins that signal the presence of a pathogen, cause innate immune cells to change their gene transcript sequences in a process mediated by an enzyme, APOBEC3A. APOBEC3A is unique in that it has previously been shown to suppress the HIV, hepatitis and HPV viruses.
"Our findings open new avenues for understanding the potential role of APOBEC3 genes in viral and chronic diseases and cancer, and may lead to the development of novel treatment approaches," says Dr. Baysal, senior author on the study.
"We have discovered the RNA editing function of the APOBEC3A enzyme," says Shraddha Sharma, PhD, a postdoctoral Research Affiliate working in Dr. Baysal's laboratory and the first author of the study. "This is just the tip of the iceberg, as we are investigating how RNA editing is regulated in immune cells and how it may help fight viral infections."
Dr. Sharma's presentation based on this research was recognized with a best poster award at the Gordon Conference in Diversifying the Transcriptome: Consequences for Development and Disease, which was held this past March in Lucca, Italy.
The paper is entitled "APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages." The research was supported in part by RPCI's Cancer Center Support Grant from the National Cancer Institute (award P30CA016056).