Molecular Biology

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Science  23 Jun 2006:
Vol. 312, Issue 5781, pp. 1717
DOI: 10.1126/science.312.5781.1717c

MicroRNAs (miRNAs) are small (20- to 22- nucleotide) RNAs that are encoded in the genomes of most plants and animals and that regulate gene expression by pairing with complementary sequences in the 3′ untranslated regions (UTRs) of target mRNAs. A perfect match between miRNA and target, as found in plants, generally results in cleavage and subsequent degradation of the target. An imperfect match, as often found in animals, generally results in repression of translation (of the mRNA into protein) and sequestration of the mRNA into cytoplasmic P bodies. Can such a repressed mRNA break free from its inhibitory miRNA and reenter the pool of active mRNAs or is it doomed to stay silenced?

Bhattacharyya et al. investigate the dynamics of miRNA regulation by analyzing miR-122-directed repression of the human cationic amino acid transporter 1 (CAT-1). In Huh7 cells, CAT-1 translation is repressed by miR-122, and CAT-1 mRNA is found in P bodies. Stressing the cells by amino acid starvation results in the movement of CAT-1 mRNA from P bodies into actively translating ribosomes and in an increase of CAT-1 protein, brought about by the release of CAT-1 mRNA from the inhibitory action of miR-122. These effects are mediated by the interaction of the AU-rich element (ARE)-binding protein HuR with a segment of the CAT-1 3′ UTR that is rich in A and U residues. Thus, miRNA-based down-regulation in animals is not all or none, as in plants, and can be reversed in response to changing conditions. — GR

Cell 125, 1111 (2006).

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