Critical roles for Dicer in the female germline

  1. Elizabeth P. Murchison1,3,
  2. Paula Stein2,3,
  3. Zhenyu Xuan1,
  4. Hua Pan2,
  5. Michael Q. Zhang1,
  6. Richard M. Schultz2,5, and
  7. Gregory J. Hannon1,4
  1. 1 Cold Spring Harbor Laboratory, Watson School of Biological Sciences and Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA;
  2. 2 Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
  1. 3 These authors contributed equally to this work.

Abstract

Dicer is an essential component of RNA interference (RNAi) pathways, which have broad functions in gene regulation and genome organization. Probing the consequences of tissue-restricted Dicer loss in mice indicates a critical role for Dicer during meiosis in the female germline. Mouse oocytes lacking Dicer arrest in meiosis I with multiple disorganized spindles and severe chromosome congression defects. Oogenesis and early development are times of significant post-transcriptional regulation, with controlled mRNA storage, translation, and degradation. Our results suggest that Dicer is essential for turnover of a substantial subset of maternal transcripts that are normally lost during oocyte maturation. Furthermore, we find evidence that transposon-derived sequence elements may contribute to the metabolism of maternal transcripts through a Dicer-dependent pathway. Our studies identify Dicer as central to a regulatory network that controls oocyte gene expression programs and that promotes genomic integrity in a cell type notoriously susceptible to aneuploidy.

Keywords

Footnotes

  • 4 Corresponding authors.

    4 E-MAIL hannon{at}cshl.edu; FAX (516) 367-8874.

  • 5 E-MAIL rschultz{at}sas.upenn.edu; FAX (215) 898-8780.

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

  • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1521307

    • Received December 5, 2006.
    • Accepted February 7, 2007.
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