MicroRNAs (miRNAs) are endogenously encoded small noncoding RNAs, derived by processing of short RNA hairpins, that can inhibit the translation of mRNAs bearing partially complementary target sequences. In contrast, small interfering RNAs (siRNAs), which are derived by processing of long double-stranded RNAs and are often of exogenous origin, degrade mRNAs bearing fully complementary sequences. Here, we demonstrate that an endogenously encoded human miRNA is able to cleave an mRNA bearing fully complementary target sites, whereas an exogenously supplied siRNA can inhibit the expression of an mRNA bearing partially complementary sequences without inducing detectable RNA cleavage. These data suggest that miRNAs and siRNAs can use similar mechanisms to repress mRNA expression and that the choice of mechanism may be largely or entirely determined by the degree of complementary of the RNA target.

Animal cells have recently been shown to express a range of approximately 22 nucleotide noncoding RNAs termed micro RNAs (miRNAs). Here, we show that the human mir-30 miRNA can be excised from irrelevant, endogenously transcribed mRNAs encompassing the predicted 71 nucleotide mir-30 precursor. Expression of the mir-30 miRNA specifically blocked the translation in human cells of an mRNA containing artificial mir-30 target sites. Similarly, designed miRNAs were also excised from transcripts encompassing artificial miRNA precursors and could inhibit the expression of mRNAs containing a complementary target site. These data indicate that novel miRNAs can be readily produced in vivo and can be designed to specifically inactivate the expression of selected target genes in human cells.