One of biology’s most talked-about breakthroughs of the past decade involves microRNAs—small, non-coding strands of RNA—and their prevalence in all living cells.

An article by RENCI and UNC-Chapel Hill researchers, soon to be published in the print version of the journal RNA, adds to the growing knowledge about microRNAs (miRNAs) and their role in adjusting or inhibiting gene expression, the term used to describe how RNA encodes information from genes and turns it into functional products, such as proteins.

“Just what we need–another layer of complexity in gene regulation!”  said RENCI Research Scientist Clark Jeffries, Ph.D., about the latest findings on miRNAs. “Most of what we know about miRNAs has been learned in the last 10 years, and because of their role as adjusters of gene expression, there is much interest in how they can help us understand and treat the genetic causes of diseases.”

Jeffries, who also holds an appointment in UNC’s Eshelman School of Pharmacy, co-authored the paper “Nuclear and cytoplasmic localization of neural stem cell microRNAs,” with Howard Fried, Ph.D., of the biophysics and biochemistry department, and Diana Perkins, M.D., MPH, of the psychiatry department. The paper was published online on March 1 at the RNA Journal website (subscription or payment required to view full text) and will appear in the next print edition of RNA.

MiRNA strands contain only about 20 individual nucleotides, the molecules that comprise RNA and DNA strands, compared to the thousands of nucleotides that make up messenger RNA (mRNA)—the RNA that carries genetic code from DNA templates to the ribosomes of cells where proteins are produced.

Researchers are interested in the properties of miRNAs because of their role as adjusters of gene expression. In principle, said Jeffries, levels of miRNAs could be altered through gene therapy or other means in order to correct dysfunctions of gene expression that characterize diseases.

MicroRNAs are first synthesized in the nucleus but modified and made ready for gene regulation in the cytoplasm. Until 2007, many scientists thought that regulatory miRNAs stayed in the cytoplasm, but a research team at Johns Hopkins University discovered that some find their way back into the nucleus.
The UNC/RENCI researchers looked at miRNAs in both the cytoplasm and the nuclei of human neural stem cells, which are believed to be capable of developing into a variety of types of brain cells.  The team made efficient use of highly accurate assays of hundreds of species of miRNAs and were able to obtain statistically significant results using only three samples of nuclear cell contents and three samples of cytoplasmic cell contents.

“That miRNAs are plentiful in neural stem cell nuclei is important,” said Jeffries. “It suggests that we could possibly correct problems with the synthesis of cellular products—an exceedingly complex chain of events—by means that are further upstream than some other approaches.”

Understanding the characteristics of these nucleus-based miRNAs in neural stem cells could lead scientists to someday create drugs that enter the nucleus and act much like miRNAs in inhibiting the production of genetic materials associated with psychiatric illnesses or diseases of the brain and nervous system, he added.

The research described in the paper is funded by the San Francisco Foundation, the Stanley Medical Research Institute, and the National Institutes of Health.