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J. Biol. Chem., Vol. 283, Issue 31, 21310-21314, August 1, 2008

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Accelerated Publication

Determinants of MicroRNA Processing Inhibition by the Developmentally Regulated RNA-binding Protein Lin28^*

From the Stem Cell Program, Children's Hospital Boston, the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and the Harvard Stem Cell Institute, Boston, Massachusetts 02115

ABSTRACT

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.

Received for publication, May 26, 2008 , and in revised form, June 11, 2008.

FOOTNOTES

^* This work was supported by laboratory start-up funds from the Children's Hospital Boston, grants from the Harvard Stem Cell Institute, and the March of Dimes Basil O'Conner Starter Scholar Research Award (to R. I. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Karp Bldg. 09212, 1 Blackfan Circle, Boston, MA 02115. Tel.: 617-919-2273; Fax: 617-730-0748; E-mail: rgregory{at}enders.tch.harvard.edu.

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