title: Selective blockade of microRNA processing by Lin28.
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.
authors.affiliation: 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.
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Viswanathan
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Richard I
authors.initials: RI
authors.lastname: Gregory
mesh_terms: D000818:Animals; D018236:Carcinoma, Embryonal; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; C488352:Lin-28 protein, mouse; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C513400:Drosha protein, mouse; D043244:Ribonuclease III