Journal
SCIENCE
Volume 320, Issue 5872, Pages 97-100Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1154040
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NIDDK NIH HHS [DK70055] Funding Source: Medline
- NIH HHS [DP1 OD000256] Funding Source: Medline
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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.
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