A new tool promises to help scientists better understand and manipulate genes whose expression is regulated by non-coding pieces of RNA termed microRNAs (miRNAs). In a study published by Nature, Markus Stoffel and colleagues show that a class of specially engineered compounds called 'antagomirs' can effectively silence the action of miRNAs in regulating gene expression.
Antagomirs are short RNA molecules that are constructed to be stable in vivo; their sequences are designed to be complementary to individual miRNAs. The antagomir binds to its specific target miRNA, and, as shown in this work, this interaction inhibits the miRNA's activity.
The team designed a version of this compound to specifically target an miRNA found only in the liver, and administered the antagomir to mice. This treatment reduced the usually abundant miRNA to undetectable levels, without any noticeable toxic effects. The group also saw a drop in plasma cholesterol levels in mice treated with the antagomir, suggesting that this miRNA normally regulates genes in the pathway that produces cholesterol. In the future, antagomirs could assist in deciphering the role of miRNAs in the control of gene expression, and be used to treat diseases that are associated with dysregulated miRNA function, such as cancer.
Markus Stoffel (Rockefeller University, New York, NY, USA)
Abstract available online.
(C) Nature press release.
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