Genetically encoded inhibitors that soak up microRNAs in mammalian cells are presented online in Nature Methods. Being able to incapacitate microRNAs provides valuable insights into their function during normal development and disease.
MicroRNAs, unlike longer messenger RNAs (mRNAs), do not contain information for making a protein, but their short, 21 nucleotide, sequences specifically regulate mRNA expression. MicroRNAs bind to partly complementary sequences on their target mRNAs and as a consequence the mRNA is either marked for decay or protein translation is inhibited. Overexpression of certain microRNAs has been linked to cancer and other diseases and a better understanding of their action is therefore important.
Philip Sharp and colleagues have developed a tool to specifically block microRNAs. The principle of their system is based on soaking up all the microRNAs with a complementary decoy sequence, so the mRNA can express its protein unhindered. In contrast to previously described chemically synthesized microRNA inhibitors, these microRNA sponges are genetically encoded. They are provided to the cell either in form of a plasmid or they are stably integrated into the genome of a cell. This provides a much higher level of control over the amount of microRNA sponges a cell produces and allows microRNA action in a specific cell or tissue type to be studied.
Philip A Sharp (Massachusetts Institute of Technology, Cambridge, MA, USA)
Abstract available online.
(C) Nature Methods press release.
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