Scientists know that short strands of RNA called microRNA (miRNA) control the expression of genes, but a City of Hope team has now shown that miRNA also play a role in epigenetic changes deep within the cell. The finding potentially expands scientists’ arsenal as they pursue gene therapies against genetic diseases such as cancer.
 Daniel Kim, front, and John Rossi study RNA interference. (Photo by Paula Myers) |
City of Hope’s John J. Rossi, Ph.D., Lidow Family Reseach Chair and senior investigator on the study, and colleagues from City of Hope and the Norwegian University of Science and Technology published the study in the Oct. 21 issue of Proceedings of the National Academy of Sciences.
Rossi, chair of the Department of Molecular Biology, has been researching gene silencing through RNA interference for more than a decade and is known for his studies into the use of short, interfering RNA (siRNA) to treat HIV.
In the most recent study, Rossi’s lab conducted research into miRNA, which is similar to siRNA but has its own unique characteristics.
In a process called gene expression, specific areas of DNA are activated to produce proteins or other molecules. Previous research found that miRNA primarily controls how much protein is created at the end of gene expression within the cytoplasm — the liquid outside the cell’s nucleus.
Now research led by Daniel Kim, Ph.D., recent graduate of the City of Hope Graduate School of Biological Sciences, confirms that miRNA also acts on the DNA within the nucleus of the cell at the beginning stages of gene expression. That may make miRNA a far more powerful therapeutic tool. Kim is now a Howard Hughes Medical Institute researcher at Harvard Medical School.
The work has specific implications for gene therapy. In this investigational technique, scientists introduce a specially modified gene into the body to fight disease by altering how the patient’s own DNA functions. Scientists know that modified versions of small RNA such as miRNA can be used in a similar way. Until now, though, they did not know much about endogenous miRNA — miRNA that originate from within the cells themselves.
“We are one of the first labs to demonstrate that endogenous miRNA can target and silence genes in mammals,” said Rossi. “We identified 10 examples of miRNA that are fully complementary to promoter regions.”
The research means that miRNA can silence, or turn off, genes and affect their expression without changing their underlying genetic code. These are called epigenetic changes.
“We now have a natural sequence for gene silencing that bears further investigation to better understand gene silencing,” said Rossi. “The more we understand how a system works, the better we can develop more targeted therapies for genetic diseases like cancer.”