Dumbbell-Shaped RNA Silences Genes

RNA molecules shaped like dumbbells can be used to trigger the gene-silencing phenomenon of RNA interference (RNAi), according to a new report (J. Am. Chem. Soc., DOI: 10.1021/ja0754453). Yoshihiro Ito, Hiroshi Abe, and Naoko Abe at the Japanese research institute RIKEN synthesized RNA molecules consisting of a double-stranded stem ranging from 15 to 27 base pairs in length that is capped with loops at both ends. Nucleotides in small interfering RNAs (siRNAs) are often modified to make them resistant to nucleic acid-degrading enzymes called nucleases, but the Japanese researchers used unmodified nucleotides. The loops nevertheless make the RNA dumbbells resistant to nuclease degradation. The dumbbell RNAs were cleaved by the Dicer enzyme to release the double-stranded RNA that activates RNAi pathways. By using RNA dumbbells with stem regions that match the firefly luciferase gene, the researchers found that the dumbbells silence luciferase expression more effectively and for a longer time than do corresponding linear siRNAs.