Everything depends, of course, on the microRNAs' targets. MicroRNAs cannot act until they have paired with complementary nucleotides on a cell's messenger RNA. Once paired, they generally shorten the lifetime of the messenger RNA, or block or weaken its instructions, thus reducing the output of protein. Now, one big push in microRNA research is to find an efficient method of zeroing in on their targets.

Several groups have developed computer programs that predict which genes are the most likely targets of each microRNA. To evaluate these programs and find targets that might be missed by the programs, researchers are also developing new methods for identifying targets.

At Stanford University, for instance, HHMI investigator Patrick O. Brown is using the kind of microarray chips he pioneered 14 years ago to examine large quantities of messenger RNA, looking for targets. Brown's results show that a program developed by Bartel and colleagues does a relatively good job of predicting the targets of the microRNAs he examined. He suggests that many segments of messenger RNA are ready to be “tuned” by specific microRNAs, as needed, in a “continuous scale of regulation.”

And former HHMI investigator Jennifer A. Doudna (now at Genentech) is attacking the problem from a different angle. Her University of California, Berkeley, lab is looking at what allows a specific microRNA to target a specific messenger RNA in terms of both nucleotide sequence and structure. “We want to harness microRNAs and manipulate them for use in therapy,” she says. “Potentially, it could have a large impact on the way drug companies develop microRNAs.”

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