MicroRNAs — the ubiquitous, short noncoding RNAs that regulate gene expression — are known to affect the levels of both messenger RNA (mRNA) and protein. But because protein production is dependent on the presence of mRNA, it has been difficult to establish the relative contributions of microRNA-mediated mRNA cleavage versus translational repression. David Bartel and colleagues have now disentangled the two mechanisms, and, contrary to expectation, find that microRNAs act mainly by destabilizing target mRNAs, rather than by inhibiting their translation. These results suggest a reassessment of many previous conclusions is in order. [Article p. 835]
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