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J Biol Chem. 2008 Aug 1;283(31):21310-4. doi: 10.1074/jbc.C800108200. Epub 2008 Jun 12.

Determinants of microRNA processing inhibition by the developmentally regulated RNA-binding protein Lin28.

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Stem Cell Program, Children's Hospital Boston, the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.


The developmentally regulated RNA-binding protein Lin28 blocks processing of let-7 family microRNAs (miRNAs) in embryonic cells. The molecular basis for this selective miRNA processing block is unknown. Here we find that Lin28 selectively binds the terminal loop region of let-7 precursors in vitro and that the loop mediates miRNA processing inhibition in vivo. Additionally, we identify the domains of Lin28 required for this inhibition. These findings establish a regulatory role for the terminal loop of precursors in miRNA maturation and provide insight into the mechanism by which Lin28 negatively regulates let-7 processing.

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