Non-Standard MicroRNA Silencing Interactions Appear More Prevalent in Human Bology Than Previously Believed, Suggesting More Complex Roles for MicroRNAs

MicroRNAs (miRNAs) regulate protein-coding gene abundance levels by interacting with the 3´ end of various messenger RNAs. Each target site matches the first few nucleotides of the targeting miRNA, the so called "seed" region, and this interaction leads to the degradation of the target or prevents its translation into amino acids. This dogma has led researchers to largely look for perfect base-pair matching of the "seed" region among candidate targets. New research published today (August 8, 2014) in Nature's open-access journal Scientific Reports suggests that non-canonical binding may be much more prevalent than previously expected, revealing a much broader array of targets for miRNAs that includes both regions that code for proteins and others that do not. "The findings may help explain why the microRNA field has run into difficulty when translating these powerful molecules into therapies for diseases ranging from cancer to diabetes," says senior author Isidore Rigoutsos, Ph.D., Director of the Computational Medicine Center in the Sidney Kimmel Medical College at Thomas Jefferson University. "There is still so much we don't know about how miRNAs work in the body." The research add to previous reports by the Jefferson group and by others demonstrating that the miRNA "targetome" – the spectrum of RNAs that miRNAs attack – is much more complex than previously anticipated. "Our study shows that even conserved miRNAs that we share with animals and insects can have very different behavior across organisms and even across different tissues in our bodies," says Dr. Rigoutsos.
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