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Selective Blockade of MicroRNA Processing by Lin28
Srinivas R. Viswanathan,1George Q. Daley,1,2*Richard I. Gregory1*
MicroRNAs (miRNAs) play critical roles in development, and dysregulationof miRNA expression has been observed in human malignancies.Recent evidence suggests that the processing of several primarymiRNA transcripts (pri-miRNAs) is blocked posttranscriptionallyin embryonic stem cells, embryonal carcinoma cells, and primarytumors. Here we show that Lin28, a developmentally regulatedRNA binding protein, selectively blocks the processing of pri-let-7miRNAs in embryonic cells. Using in vitro and in vivo studies,we found that Lin28 is necessary and sufficient for blockingMicroprocessor-mediated cleavage of pri-let-7 miRNAs. Our resultsidentify Lin28 as a negative regulator of miRNA biogenesis andsuggest that Lin28 may play a central role in blocking miRNA-mediateddifferentiation 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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