Cited by 755

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

Thomson, J. Michael, Newman, Martin, Parker, Joel S., Morin-Kensicki, Elizabeth M., Wright, Tricia, Hammond, Scott M.·2006·Genes & Development

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.

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  1. Eis, P.S., Tam, W., Sun, L., Chadburn, A., Li, Z., Gomez, M.F., Lund, E., and Dahlberg, J.E. 2005. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc. Natl. Acad. Sci. 102: 3627-3632.
  2. Ramaswamy, S., Tamayo, P., Rifkin, R., Mukherjee, S., Yeang, C.H., Angelo, M., Ladd, C., Reich, M., Latulippe, E., Mesirov, J.P., et al. 2001. Multiclass cancer diagnosis using tumor gene expression sig- natures. Proc. Natl. Acad. Sci. 98: 15149-15154.

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Authors
Thomson, J. M., Newman, M., Parker, J. S., Morin-Kensicki, E. M., Wright, T., & Hammond, S. M.
Venue
Genes & Development
Published
2006-08-01
Volume
20
Issue
16
Pages
2202-2207
ISSN
  • 0890-9369
  • 1549-5477
Cited by
755
References
2
Language
en

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