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Molecular and Cellular Biology, June 2007, p. 3970-3981, Vol. 27, No. 11
0270-7306/07/$08.00+0     doi:10.1128/MCB.00128-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

P-Body Formation Is a Consequence, Not the Cause, of RNA-Mediated Gene Silencing{triangledown} ,{dagger}

Ana Eulalio, Isabelle Behm-Ansmant, Daniel Schweizer, and Elisa Izaurralde*

MPI for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany

Received 19 January 2007/ Returned for modification 16 February 2007/ Accepted 19 March 2007

P bodies are cytoplasmic domains that contain proteins involved in diverse posttranscriptional processes, such as mRNA degradation, nonsense-mediated mRNA decay (NMD), translational repression, and RNA-mediated gene silencing. The localization of these proteins and their targets in P bodies raises the question of whether their spatial concentration in discrete cytoplasmic domains is required for posttranscriptional gene regulation. We show that processes such as mRNA decay, NMD, and RNA-mediated gene silencing are functional in cells lacking detectable microscopic P bodies. Although P bodies are not required for silencing, blocking small interfering RNA or microRNA silencing pathways at any step prevents P-body formation, indicating that P bodies arise as a consequence of silencing. Consistently, we show that releasing mRNAs from polysomes is insufficient to trigger P-body assembly: polysome-free mRNAs must enter silencing and/or decapping pathways to nucleate P bodies. Thus, even though P-body components play crucial roles in mRNA silencing and decay, aggregation into P bodies is not required for function but is instead a consequence of their activity.

* Corresponding author. Mailing address: Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany. Phone: 49-70 71-601-1350. Fax: 49-70 71-601-1353. E-mail: elisa.izaurralde{at}tuebingen.mpg.de

{triangledown} Published ahead of print on 2 April 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, June 2007, p. 3970-3981, Vol. 27, No. 11
0270-7306/07/$08.00+0     doi:10.1128/MCB.00128-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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