The article explores the mechanisms by which microRNAs (miRNAs) and small interfering RNAs (siRNAs) can inhibit mRNA expression. MiRNAs, derived from short RNA hairpins, can inhibit mRNA translation through partially complementary target sequences, while siRNAs, derived from long double-stranded RNAs, degrade mRNAs with fully complementary sequences. The study demonstrates that endogenously encoded human miRNAs can cleave mRNAs with fully complementary target sites, whereas exogenously supplied siRNAs can inhibit mRNA expression with partially complementary sequences without inducing detectable RNA cleavage. These findings suggest that miRNAs and siRNAs may use similar mechanisms to repress mRNA expression, with the choice of mechanism determined by the degree of complementary between the RNA target and the miRNA or siRNA. The study also highlights the functional interchangeability of miRNAs and siRNAs in cultured human cells, supporting the hypothesis that their effects on mRNA fate are largely determined by the complementarity of the target sequence.The article explores the mechanisms by which microRNAs (miRNAs) and small interfering RNAs (siRNAs) can inhibit mRNA expression. MiRNAs, derived from short RNA hairpins, can inhibit mRNA translation through partially complementary target sequences, while siRNAs, derived from long double-stranded RNAs, degrade mRNAs with fully complementary sequences. The study demonstrates that endogenously encoded human miRNAs can cleave mRNAs with fully complementary target sites, whereas exogenously supplied siRNAs can inhibit mRNA expression with partially complementary sequences without inducing detectable RNA cleavage. These findings suggest that miRNAs and siRNAs may use similar mechanisms to repress mRNA expression, with the choice of mechanism determined by the degree of complementary between the RNA target and the miRNA or siRNA. The study also highlights the functional interchangeability of miRNAs and siRNAs in cultured human cells, supporting the hypothesis that their effects on mRNA fate are largely determined by the complementarity of the target sequence.