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Volume 140, Issue 4, 19 February 2010, Pages 445-449 doi:10.1016/j.cell.2010.02.007?|?How to Cite or Link Using DOI? ??Permissions Reprints Essay Lin28: A MicroRNA Regulator with a Macro Role Srinivas R. Viswanathan1 and George Q. Daley1, , 1 Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Childrens Hospital Boston and Dana Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and the Howard Hughes Medical Institute, Boston, MA 02115, USA Available online 18 February 2010. Lin28, a highly conserved RNA-binding protein, has emerged as a modulator of the processing of the let-7 microRNA. This role for Lin28 has important implications for our mechanistic understanding of pluripotency, the timing of development, and oncogenesis. Article Outline Main Text Lin28, Reprogramming, and Pluripotency Lin28 and Cancer Lin28: A Developmental Regulator Acknowledgements References Main Text MicroRNAs (miRNAs) are a class of small RNAs with diverse regulatory roles. The discovery of miRNAs and closely related small-interfering RNAs (siRNAs) is a watershed moment in biology that has changed traditional views of genetic regulation and has placed small RNAs alongside transcription factors as critical regulators of gene expression. But what regulates these regulators? Recent studies indicate that miRNA biogenesis can be posttranscriptionally regulated by trans-acting factors. The Lin28/let-7 partnership is the best characterized example of the relationship between an miRNA and its posttranscriptional regulator and may shed light on the posttranscriptional regulation of other miRNAs. Here, we highlight recent advances in our understanding of the posttranscriptional regulation of the let-7 miRNA by the conserved RNA-binding protein Lin28 and show how this impacts our understanding of pluripotency, development, and cancer. Lin28 was first characterized in the nematode Caenorhabditis elegan