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  • Review Article
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P bodies: at the crossroads of post-transcriptional pathways

Nature Reviews Molecular Cell Biology volume 8, pages 9–22 (2007)Cite this article

Key Points

  • P bodies are discrete cytoplasmic domains in which proteins that are involved in mRNA degradation, translational repression, mRNA surveillance and RNA-mediated gene silencing colocalize.

  • Key features of P bodies have been conserved throughout evolution. First, P-body assembly is dependent on RNA — treating cells with ribonucleases leads to the dispersion of P bodies. Second, the size and number of P bodies depends on the fraction of mRNAs that are undergoing decapping. Blocking mRNA decay at an early stage (for example, by preventing deadenylation) leads to P-body loss, whereas blocking decapping leads to an increase in the size and number of P bodies. Last, P bodies are dispersed by drugs that stabilize polysomes (for example, cycloheximide) and are enhanced by drugs that release ribosomes from mRNA (for example, puromycin). Therefore, mRNAs must exit the translation cycle to enter into P bodies.

  • The available evidence indicates that mRNA decay, translational repression and mRNA silencing can take place in P bodies. However, it is still unclear whether the integrity of P bodies is required for these processes to occur or whether P bodies arise as a consequence of these activities.

  • P bodies share common components with other messenger ribonucleoprotein (mRNP) granules that are present in stressed mammalian cells (stress granules), in polarized cells such as neurons, and during oogenesis in diverse organisms (polar granules).

Abstract

Post-transcriptional processes have a central role in the regulation of eukaryotic gene expression. Although it has been known for a long time that these processes are functionally linked, often by the use of common protein factors, it has only recently become apparent that many of these processes are also physically connected. Indeed, proteins that are involved in mRNA degradation, translational repression, mRNA surveillance and RNA-mediated gene silencing, together with their mRNA targets, colocalize within discrete cytoplasmic domains known as P bodies. The available evidence indicates that P bodies are sites where mRNAs that are not being translated accumulate, the information carried by associated proteins and regulatory RNAs is integrated, and their fate — either translation, silencing or decay — is decided.

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Figure 1: P bodies in Drosophila melanogaster Schneider cells.
Figure 2: Molecular link between NMD and P bodies.
Figure 3: Model for P-body assembly.

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Acknowledgements

We are grateful to D.J. Thomas for comments on the manuscript. This study was supported by the Max Planck Society and the Human Frontier Science Program Organization (HFSPO). A.E. and I.B-A. are recipients of fellowships from the Portuguese Foundation for Science and Technology and the European Molecular Biology Organization (EMBO), respectively.

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  1. Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen, D-72076, Germany

    Ana Eulalio, Isabelle Behm-Ansmant & Elisa Izaurralde

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  1. Ana Eulalio
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Glossary

Ribonucleoprotein

(RNP). A complex of proteins and RNA. In many cases, the proteins bind directly to their cognate mRNA molecules (mRNPs). Proteins can also be recruited to the RNP particle through protein–protein interactions.

5′→3′ exoribonuclease

An enzyme that has an important role in all aspects of RNA metabolism. It degrades RNA to 5′ mononucleotides in a 5′→3′ direction.

5′-cap structure

A structure that consists of m7GpppN (where m7G represents 7-methylguanylate, p represents a phosphate group and N represents any base) that is located at the 5′ end of a eukaryotic mRNA.

Decapping

The process of removing the 5′-cap structure from an mRNA, usually as a step prior to further 5′→3′-exonucleolytic digestion of the remainder of the mRNA. In eukaryotes, decapping is catalysed by the decapping enzyme DCP2 assisted by decapping co-activators such as DCP1, EDC3 and the LSm1–7 complex.

Deadenylase

An enzyme that catalyses the degradation of the 3′-poly(A) tail, which is present on most eukaryotic mRNAs. Although many deadenylases have been described, the principal cytoplasmic activity in yeast seems to reside in the CCR4–CAF1–NOT complex.

Exosome

A complex of at least 11 putative 3′→5′ exonucleases that functions in several different RNA-processing and RNA-degradation pathways in the nucleus and the cytoplasm.

Nonsense-mediated mRNA decay

(NMD). The process by which the cell destroys mRNAs, the translation of which has been prematurely terminated owing to the presence of a nonsense codon within the coding region.

Premature translation-termination codon

(PTC). An alternative name for a nonsense codon. An in-frame stop codon that terminates translation, which leads to C-terminal truncated proteins. PTCs elicit NMD.

Small interfering RNA

(siRNA). A non-coding RNA of ∼22 nucleotides that is processed from a longer dsRNA during RNA interference. Such non-coding RNAs base pair with mRNA targets and confer target specificity on the silencing complexes in which they reside.

microRNA

(miRNA). A small RNA of ∼22 nucleotides that is encoded by an endogenous gene. The miRNA regulates the expression of RNAs to which it is complementary in sequence.

Argonaute proteins

A family of proteins that are characterized by the presence of two homology domains, PAZ and PIWI. These proteins are essential for diverse RNA-silencing pathways.

RNA-induced silencing complex

(RISC). A complex that consists minimally of an Argonaute protein and the associated miRNA or siRNA. The RISC complex mediates miRNA- or siRNA-guided gene silencing.

PIWI domain

A conserved protein domain that is found in members of the Argonaute-protein family. It is structurally similar to ribonuclease-H domains and, in at least some cases, has endoribonuclease activity.

Polysome

Two or more ribosomes that are bound to different sites on the same mRNA.

Nurse cell

An auxiliary cell that supplies the oocyte with synthesized mRNAs and proteins during insect oogenesis.

Dicer

An RNase III-type nuclease that is required for the processing of double-stranded-RNA precursors into siRNAs.

ARE-mediated mRNA decay

(AMD). A process of rapid degradation of mRNAs that harbour A- and U-rich sequence elements (AREs) that are generally located in the 3′-untranslated region of the mRNA.

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Eulalio, A., Behm-Ansmant, I. & Izaurralde, E. P bodies: at the crossroads of post-transcriptional pathways. Nat Rev Mol Cell Biol 8, 9–22 (2007). https://doi.org/10.1038/nrm2080

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