Eukaryotic gene expression involves several post- transcriptional events that share mRNA as a common substrate 1–3 . The primary transcript is processed by the removal of introns and the addition of a poly(A) tail, and the mature mRNA is exported from the nucleus to the cytoplasm for translation. Not all mRNAs are translated immediately; some are maintained in a trans- lationally repressed state and might be transported to a specific cytoplasmic location where translation might be activated. In the cytoplasm, mRNAs are also subject to quality control and regulatory mechanisms that either promote mRNA degradation or repress mRNA trans- lation. Translational repression and mRNA decay can be triggered by specific RNA-binding proteins and also by small, complementary regulatory RNAs in a process known as RNA-mediated gene silencing. Eventually, the mRNAs are degraded. In eukaryotes, hundreds of proteins and small non- coding RNAs participate in post-transcriptional processes and their regulation. Many act on bulk mRNA, whereas others regulate specific transcripts. A subset of these factors, with functions in translational repression, mRNA silencing, mRNA surveillance (or quality control) and degradation, colocalize in discrete cytoplasmic domains referred to as mRNA-processing bodies (now known as P bodies), which reveals fundamental interrelationships among these processes. In this review, we focus on the role of P bodies in mRNA surveillance and mRNA decay, RNA-mediated silencing and translational control. We also discuss cur- rent models of P-body function and the link between P bodies and other messenger ribonucleoprotein (mRNP) granules that are present in stressed mammalian cells, in polarized cells such as neurons, and during oogenesis in diverse organisms. Discovery and rediscovery of P bodies In 1997, Bashkirov et al. 4 reported that XRN1, the main cytoplasmic 5′→3′ exoribonuclease in eukaryotic cells, was localized in small granular structures and was “highly enriched in discrete, prominent foci” within the cytoplasm of mammalian cells. This observation, the biological importance of which remained unappreciated for almost five years, paved the way for fundamental discoveries in the field of RNA metabolism and post- transcriptional gene regulation. Insights into the role of the XRN1 foci as sites where eukaryotic mRNA degrada- tion can take place emerged from the discovery that the enzyme that cleaves the 5′-cap structure of mRNA (the decapping enzyme DCP2) and its cofactors colocalize with XRN1 in these foci in both mammalian and yeast cells 5–9 . The decapping enzyme functions upstream of XRN1 in the 5′→3′ mRNA-decay pathway (BOX 1); it hydrolyses the cap structure leaving an mRNA with a 5′ monophosphate, which is the preferred substrate for XRN1. The foci were called P bodies, DCP bodies or mRNA-decay foci. XRN1 foci were rediscovered in 2002 by Eystathioy et al. 10 thanks to an autoimmune serum from a patient who suffered from motor and sensory neuropathy. This serum stained discrete cytoplasmic domains and rec- ognized a novel human protein of unknown function, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany. Correspondence to E.I. e-mail: elisa.izaurralde@ tuebingen.mpg.de doi:10.1038/nrm2080 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 m 7 GpppN (where m 7 G represents 7-methylguanylate, p represents a phosphate group and N represents any base) that is located at the 5′ end of a eukaryotic mRNA. P bodies: at the crossroads of post-transcriptional pathways Ana Eulalio, Isabelle Behm-Ansmant and Elisa Izaurralde 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. NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 8 | JANUARY 2007 | 9 REVIEWS © 2007 Nature Publishing Group