Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing
Abstract
A hallmark of mammalian embryonic development is the widespread induction of microRNA (miRNA) expression. Surprisingly, the transcription of many of these small, noncoding RNAs is unchanged through development; rather, a post-transcriptional regulatory event prevents accumulation of the mature miRNA species. Here, we present a biochemical framework for the regulated production of the Let-7 family of miRNAs. Embryonic cells contain a Drosha Inhibitor that prevents processing of the Let-7 primary transcript. This inhibitor specifically binds to conserved nucleotides in the loop region of the Let-7 precursor, and competitor RNAs that mimic the binding site restore Let-7 processing. We have identified the Drosha Inhibitor as the embryonic stem cell specific protein Lin-28. Lin-28 has been previously implicated in developmental regulatory pathways in Caenorhabditis elegans, and it promotes reprogramming of human somatic cells into pluripotent stem cells. Our findings outline a microRNA post-transcriptional regulatory network and establish a novel role for the miRNA precursor loop in the regulated production of mature Let-7.
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Footnotes
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Reprint requests to: Scott M. Hammond; Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA; e-mail: Hammond{at}med.unc.edu; fax: (919) 966-1856.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1155108.
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- Received April 23, 2008.
- Accepted May 7, 2008.
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Freely available online through the open access option.
- Copyright © 2008 RNA Society