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Science 320 (5872): 97-100

Copyright © 2008 by the American Association for the Advancement of Science

Selective Blockade of MicroRNA Processing by Lin28

Srinivas R. Viswanathan,1 George Q. Daley,1,2* Richard I. Gregory1*

Abstract: MicroRNAs (miRNAs) play critical roles in development, and dysregulation of miRNA expression has been observed in human malignancies. Recent evidence suggests that the processing of several primary miRNA transcripts (pri-miRNAs) is blocked posttranscriptionally in embryonic stem cells, embryonal carcinoma cells, and primary tumors. Here we show that Lin28, a developmentally regulated RNA binding protein, selectively blocks the processing of pri-let-7 miRNAs in embryonic cells. Using in vitro and in vivo studies, we found that Lin28 is necessary and sufficient for blocking Microprocessor-mediated cleavage of pri-let-7 miRNAs. Our results identify Lin28 as a negative regulator of miRNA biogenesis and suggest that Lin28 may play a central role in blocking miRNA-mediated differentiation in stem cells and in certain cancers.

1 Stem Cell Program, Children's Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA.
2 Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute; and Howard Hughes Medical Institute, Division of Hematology, Brigham and Women's Hospital, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: rgregory{at}enders.tch.harvard.edu (R.I.G.); george.daley{at}childrens.harvard.edu (G.Q.D.)


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