Circular RNA Surprise

Previously enigmatic circular RNAs have been found to influence gene expression by binding to and blocking another class of regulatory RNA, the microRNAs.

By | February 28, 2013

WIKIMEDIA COMMONS, VOSSMANSome circular RNA molecules serve as molecular “sponges,” binding to and deactivating gene modulators called microRNAs to influence gene expression, according to two papers published this week (February 27) in Nature. The findings reveal a hidden world of previously unexplored RNA molecules, and act as a reminder that there is more to RNA than simply being a messenger between DNA and the proteins it encodes.

Over the past 20 years, scientists have discovered a series of unexpected forms of RNA, from the unusually short and long to those that blocked other RNA strands from being translated into proteins. But because typical RNA sequencing approaches work by detecting molecules with tails, circular RNAs, whose ends are joined together, went unnoticed. Now, however, new sequencing methods are revealing the existence and function of circular RNA in nematodes, mice, and humans.

“It’s yet another terrific example of an important RNA that has flown under the radar,” Erik Sontheimer, a molecular biologist at Northwestern University in Evanston, Illinois, told Nature. “You just wonder when these surprises are going to stop.”

Looking at a circular RNA expressed in the brains of humans and mice, researchers at Aarhus University in Denmark, found that the molecules blocked a microRNA called miR-7 that usually inhibits gene expression of certain messenger RNAs. So the circular RNA was suppressing the activity of the blocker, resulting in an increase in expression of miR-7’s target genes.

Circular RNAs could also act as sponges for microRNA originating outside the cell, as some have possible binding sites for viral microRNAs. “They are so abundant, there are probably a multitude of functional roles,” Julia Salzman, a molecular biologist at Stanford University School of Medicine in California who was not involved in the study, told Nature.

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