P-body formation is a consequence, not the cause, of RNA-mediated gene silencing.
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.
Eulalio
Ana
A
Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany.
Behm-Ansmant
Isabelle
I
Schweizer
Daniel
D
Izaurralde
Elisa
E
D000818:Animals; D022083:Cytoplasmic Structures / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; C516259:TRAL protein, Drosophila