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Chem Biol. 2004 Dec;11(12):1619-23.

Architecture of a validated microRNA::target interaction.

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Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.


MicroRNAs are small approximately 22 nucleotide regulators of numerous biological processes and bind target gene messenger RNAs to control gene expression. The C. elegans microRNA let-7 and its target lin-41 were the first microRNA::target interaction to be validated in vivo. let-7 molecules form imperfect duplexes with two required let-7 complementary sites in the lin-41 3' UTR. Here, we show that base pairing at both the 5' and 3' ends of the let-7 binding site, as well as the presence of unpaired RNA residues in the predicted duplexes, are required for lin-41 downregulation. In this study, our model for microRNA::target interactions also demonstrates that the context of a microRNA binding can be critical for function, revealing an unforeseen complexity in microRNA::target interactions.

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