When Cells Reach Out and Touch: RNA Production Revs Up During CelltoCell Contact.

(From AScribe)

BALTIMORE -- MicroRNAs are single-stranded snippets that, not long ago, were given short shrift as genetic junk. Now that studies have shown they regulate genes involved in normal functioning as well as diseases such as cancer, everyone wants to know: What regulates microRNAs?

Scientists at Johns Hopkins were surprised to find an elegantly simple answer: touch. In a new study, published online April 9 in the Proceedings of the National Academy of Sciences, the researchers discovered that cell-to-cell contact revs up the manufacture of these small but mighty molecules.

"This study documents one of the very few clear examples of a stimulus that directly influences the global efficiency of microRNA production," says Josh Mendell, M.D., Ph.D., an assistant professor in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. "No one anticipated, including us, that the production of microRNAs is linked to how densely cells are packed together."

In what Mendell describes as an "accidental discovery," the team was studying contact inhibition: a phenomenon in which non-cancerous cells growing in a dish stop multiplying when they touch each other. Cancer cells, on the other hand, lose contact inhibition and continue to proliferate even when they're touching. The researchers suspected that microRNAs might play a role in contact inhibition because whenever they studied these enigmatic bits -- only about 20 or so genetic building blocks comprise a microRNA -- they always saw more in the tissues of animals, where cells are packed together, relative to the amount they found in isolated cells growing in culture.

To investigate, the team grew cancer cells and non-cancer cells to increasing densities in culture and, using a tool developed in the Mendell laboratory, measured the abundance of hundreds of microRNAs simultaneously. This analysis revealed that the more densely the cells were packed together, the more microRNA was produced in each cell.

The scientists then examined microRNA production in five additional commonly studied human and mouse cell lines, including human breast cancer cells, human colorectal cancer cells and human pancreatic cancer cells. They also tested fruit fly cells to determine whether or not the phenomenon is restricted to mammals.