Molecular Biology

MicroRNA Monkey Wrench

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Science  12 Mar 2004:
Vol. 303, Issue 5664, pp. 1583
DOI: 10.1126/science.303.5664.1583c

Hundreds of microRNAs (miRNAs) have been discovered in the genomes of almost all eukaryotes studied. Indeed, the predicted fraction of miRNAs in the human genome is similar to that of transcription factors, yet the functions of only a handful of these miRNAs are known. Sequence-based bioinformatics analyses suggest that miRNAs are involved in many critical cellular and developmental functions. Understanding the role of miRNAs would be helped by the ability to eliminate their function genetically—a process complicated both by their small size and by the fact that multiple miRNAs have identical or very similar sequences, potentially requiring multiple knockouts.

Hutvágner et al. and Meister et al. have both developed an antisense-based method to efficiently and irreversibly inactivate specific miRNAs. The trick is to make an oligonucleotide complementary to the miRNA and then modify it with a 2'-O-methyl group. This renders the oligo resistant to degradation, yet allows it to rapidly and stably hybridize with its miRNA target. Using this method, specific miRNAs could be knocked out irreversibly and with high efficiency in vitro, in tissue culture cells, and in whole organisms. — GR

PLOS Biol. 2, 10.1371/journal.pbio.0020114 (2004); RNA 10, 544 (2004).

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