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Selective Blockade of MicroRNA Processing by Lin28
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Journal Article
Selective Blockade of MicroRNA Processing by Lin28
2008
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Biological and medical sciences
/ Cancer
/ Cells
/ DNA-Binding Proteins - metabolism
/ Embryonic Stem Cells - cytology
/ Embryonic Stem Cells - metabolism
/ Embryos
/ Fundamental and applied biological sciences. Psychology
/ Humans
/ Mice
/ MicroRNA
/ Molecular and cellular biology
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - metabolism
/ Proteins
/ Ribonuclease III - metabolism
/ RNA
/ RNA Processing, Post-Transcriptional
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ Transcription. Transcription factor. Splicing. Rna processing
