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Genes & Dev. 20 (16): 2202-2207

Copyright © 2006 by Cold Spring Harbor Laboratory Press.

RESEARCH COMMUNICATION

Extensive post-transcriptional regulation of microRNAs and its implications for cancer

J. Michael Thomson1, Martin Newman1, Joel S. Parker4, Elizabeth M. Morin-Kensicki1, Tricia Wright2, and Scott M. Hammond1,3,5

1 Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA;
2 Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA;
3 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA;
4 Constella Group, Durham, North Carolina 27713, USA

Abstract: MicroRNAs (miRNAs) are short, noncoding RNAs that post-transcriptionally regulate gene expression. While hundreds of mammalian miRNA genes have been identified, little is known about the pathways that regulate the production of active miRNA species. Here we show that a large fraction of miRNA genes are regulated post-transcriptionally. During early mouse development, many miRNA primary transcripts, including the Let-7 family, are present at high levels but are not processed by the enzyme Drosha. An analysis of gene expression in primary tumors indicates that the widespread down-regulation of miRNAs observed in cancer is due to a failure at the Drosha processing step. These data uncover a novel regulatory step in miRNA function and provide a mechanism for miRNA down-regulation in cancer.

Key Words: miRNA • microRNA • let-7 • RISC • Drosha • cancer

Received for publication April 27, 2006. Accepted for publication June 14, 2006.

5 Corresponding author.

E-MAIL hammond{at}med.unc.edu; FAX (919) 966-1856.

Supplemental material is available at http://www.genesdev.org.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1444406.

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