Selective Blockade of MicroRNA Processing by Lin28
Copyright policy )Selective Blockade of MicroRNA Processing by Lin28
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.
- Harvard University United States
- Boston Children's Hospital United States
- Brigham and Women's Faulkner Hospital United States
- Howard Hughes Medical Institute United States
- Harvard Stem Cell Institute, Cambridge, MA, USA United States
Pluripotent Stem Cells, Ribonuclease III, Down-Regulation, RNA-Binding Proteins, Cell Differentiation, Cellular Reprogramming, Transfection, Up-Regulation, DNA-Binding Proteins, Mice, MicroRNAs, Carcinoma, Embryonal, Cell Line, Tumor, Animals, Humans, RNA Interference, RNA Processing, Post-Transcriptional, Embryonic Stem Cells, Cell Line, Transformed, Protein Binding
Pluripotent Stem Cells, Ribonuclease III, Down-Regulation, RNA-Binding Proteins, Cell Differentiation, Cellular Reprogramming, Transfection, Up-Regulation, DNA-Binding Proteins, Mice, MicroRNAs, Carcinoma, Embryonal, Cell Line, Tumor, Animals, Humans, RNA Interference, RNA Processing, Post-Transcriptional, Embryonic Stem Cells, Cell Line, Transformed, Protein Binding
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