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Fewer oocytes are produced in flies lacking Dicer-1 activity (bottom).

RUOHOLA-BAKER/MACMILLAN

Stem cells use the miRNA pathway to drive mitosis forward through a stage when other cells would stall, according to results from Steven Hatfield, Halyna Shcherbata, Hannele Ruohola-Baker (University of Washington, Seattle, WA), and colleagues.

The remarkable ability of stem cells to divide relentlessly while surrounding cells are quiescent is key to their function. Stems cells have been noted to express specific miRNAs, suggesting that translational inhibition by these small RNAs might be involved. Ruohola-Baker's group now shows that Dicer-1, the enzyme that makes miRNAs, is required for the strong proliferative capability of germline stem cells (GSCs) in flies.Compared with the wild type, mutant GSCs lacking Dicer-1 were blocked at the G1-to-S transition. Cyclin E, which normally drives cells into S phase, was high in the mutant GSCs. But Dacapo, a cyclin E inhibitor, was also elevated. As a result of the reduced GSC proliferation, female mutants made only 20% of the normal number of eggs. Egg production could be partially rescued in the Dicer-1 mutants by reducing Dacapo levels.

As Dacapo has several putative miRNA-binding sites in its 3′ UTR, the authors suspect that these miRNAs normally down-regulate Dacapo in GSCs, when other cell types become quiescent. The group is now testing whether the relevant miRNAs inhibit the translation of a reporter linked to the Dacapo 3′ UTR. Other stem cells, and possibly even cancer cells, might use a similar strategy to proliferate beyond the norm.

Reference:

Hatfield, S.D., et al. 2005. Nature. doi:.