Skip to content


  • Commentary
  • Open Access

Yeast processing bodies and stress granules: self-assembly ribonucleoprotein particles

Microbial Cell Factories201110:73

  • Received: 4 August 2011
  • Accepted: 24 September 2011
  • Published:


Processing bodies (PBs) and stress granules (SGs) are two highly conserved cytoplasmic ribonucleoprotein foci that contain translationally repressed mRNAs together with proteins from the mRNA metabolism. Interestingly, they also share some common features with other granules, including the prokaryotic inclusion bodies. Although the function of PBs and SGs remains elusive, major advances have been done in unraveling their composition and assembly by using the yeast Saccharomyces cerevisae.


  • processing bodies
  • P-bodies
  • stress granules
  • RNA granules


A growing body of evidence indicates that aggregation of proteins and ribonucleoproteins (RNPs) play a central role in cell biology. It has long been known that cytoplasmic RNP granules containing translationally repressed mRNAs exist in germ cells [1]. Two additional ubiquitous cytoplasmic RNP granules have been recently discovered in somatic cells: the processing bodies (PBs) and the stress granules (SGs) (extensively reviewed in [24]). These granules are conserved throughout evolution and are found in yeast, plant, nematode, fly, and mammalian cells. Although they have not yet been observed in prokaryotes, they are found in chloroplasts, organelles of bacterial origin, suggesting that similar structures might also assemble in prokaryotes [5]. PBs contain translationally repressed mRNAs together with proteins from the mRNA decay machinery and, in metazoans, from the miRNA machinery as well. In contrast, SGs contain mRNAs that, although they are also translationally repressed, are stalled in the process of translation initiation, together with translation initiation factors and ribosomal subunits. Both types of granules are highly dynamic and are formed in response to conditions that result in translational repression, including many types of environmental stresses, although PBs are also present in low numbers under normal cell growth [6, 7].

Studies in the yeast Saccharomyces cerevisiae have been crucial in unraveling PB biology. In yeast, these granules contain a highly conserved set of proteins that belong to the 5' deadenylation-dependent mRNA decay pathway, such as the decapping complex Dcp1/Dcp2, the decapping activators Dhh1, Pat1, Edc3, and Lsm1-7, and the 5'-3'-exonuclease Xrn1p [8]. They also harbor components of the nonsense mediated decay pathway, which rapidly degrades aberrant mRNAs that contain premature stop codons [9]. Since ribosomal subunits are not found in PBs, the mRNPs must be free of ribosomes prior to assemble into PBs [7, 10]. Several observations indicate that these mRNAs are also degraded in PBs, since these structures concentrate decapping factors as well as the decay intermediates [11]. However, not all mRNAs that localize in PBs are degraded, as mRNAs have been shown to be able to exit PBs and reinitiate translation [10]. The processes that determine whether an mRNA will be degraded, or sent back into the translation pathway, are not yet understood and are currently the focus of intense research. In addition to ribosome-free mRNAs, two proteins, Edc3 and Lsm4, are also central for PB assembly. Edc3 is a scaffolding protein with a self-aggregation domain, and Lsm4 contains a glutamine/asparagine (Q/N)-rich prion-like domain [1215]. Similar to the Q/N-rich domains found in prions, the Q/N-rich motif of Lsm4 domain self-aggregates; however, this aggregation is quickly reversible [12].

In contrast to PBs, yeast SGs harbor multiple components of the translation initiation machinery, although their composition varies depending on the type of stress. For example, SGs assembled after glucose deprivation contain eIF4E, eIF4G, Pab1, Pub1, Ngr1 and Pbp1 [1618], while those induced by severe heat shock contain 40S and eIF3, which are absent from the previous ones [18, 19]. The presence of these factors suggests that translationally repressed mRNPs assembled into SGs are stalled at a step in translation initiation that occurs after the recruitment of a subset of the translation initiation machinery [2, 4]. Importantly, PBs and SGs interact with each other, probably through shared protein components and mRNA species, and SGs are usually formed either next to or overlapping with PBs [1619]. These dynamic interactions suggest a cytoplasmic mRNP cycle model in which the mRNAs are exchanged between polysomes, SGs, and PBs, to be translated, stored, or degraded [2, 4, 18].

Although great advances have been achieved in understanding the composition and assembly of PBs and SGs, their functional significance remains unclear. Elucidating this is especially daunting since basal control of translational repression and mRNA degradation can occur even in the absence of visible PBs and SGs [12, 18, 20, 21]. However, the fact that these granules are evolutionarily conserved strongly suggests that aggregating into larger structures does confer some advantage to the cell, and that these aggregates are functionally important. It has been suggested that aggregates represent a strategy for: i) concentrating enzymes and factors that act successively to optimize the overall processes, ii) sequestering mRNA decay enzymes and thus allowing the decay kinetics to be modulated, and/or iii) preventing repressed mRNAs to compete for the translation machinery [2, 3]. Defining these functions is a crucial task that will be of fundamental interest not only for understanding PBs and SGs but also other mRNP granules, since it can be expected that they all function through similar mechanisms.

Formation of microscopic aggregates is not an exclusive function of RNP granules. Many other types of protein granules exist in the cell. For instance, novel and exciting findings show that prokaryotic inclusion bodies (IBs), which were previously believed to be composed solely of misfolded proteins, also contain active polypeptides [2224]. In eukaryotes, further examples of protein granules are the "purinosome", a multi-enzyme complex in which the enzymes involved in the de novo purine biosynthesis dynamically aggregate in response to low purine levels [25, 26], and the "eIF2B bodies", in which the translation initiation factors eIF2 and eIF2B are concentrated and which are suggested to be sites of guanine nucleotide exchange [27, 28]. In all cases, a dynamic compartmentalization of the cytosol may optimize the function of the aggregated components.

Understanding the still unclear molecular processes leading to the inclusion of mRNPs or proteins into localized foci could have fundamental practical implications in clinical research and in biotechnology. For example, aggresomes, misfolded protein aggregates that are frequently found in neurodegenerative disorders, share some striking similarities with SGs. They share several components and assembly mechanisms, which are mediated by protein-protein aggregation domains. One crucial difference, however, is that SGs are transient and dynamic, whereas aggresomes are static and long-lived [29, 30] and references therein]. Interestingly, aggresomes are reminiscent of the prokaryotic IBs. It has recently been reported that IBs can also house self-assembled and highly stable aggregates that have amyloid- or prion-like origins [31]. Thus, bacterial cells could potentially be a valuable tool to study the rules governing protein aggregation in neuronal diseases [32]. On the other hand, the latest advances in artificial engineering of nanoparticles are very promising and have already resulted in highly tunable tools [33, 34]. These nanoparticles involve the use of self-assembling peptide sequences to build modular structures that can accommodate a variety of molecules of medical interest. Along this line of reasoning, one could envisage exploiting microbial cell factories to artificially build mRNP aggregates as a way to deliver specific translationally repressed mRNAs, which could then be translated in their recipient cells, thereby tackling diseases by directly modulating protein levels.



We appreciate the financial support received from the Spanish Ministerio de Ciencia e Innovación (grant BFU2010-20803).

Authors’ Affiliations

Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain


  1. Anderson P, Kedersha N: RNA granules. J Cell Biol. 2006, 172 (6): 803-808. 10.1083/jcb.200512082.View ArticleGoogle Scholar
  2. Erickson SL, Lykke-Andersen J: Cytoplasmic mRNP granules at a glance. J Cell Sci. 2011, 124 (Pt 3): 293-297.View ArticleGoogle Scholar
  3. Balagopal V, Parker R: Polysomes, P bodies and stress granules: states and fates of eukaryotic mRNAs. Curr Opin Cell Biol. 2009, 21 (3): 403-408. 10.1016/ ArticleGoogle Scholar
  4. Buchan JR, Parker R: Eukaryotic stress granules: the ins and outs of translation. Mol Cell. 2009, 36 (6): 932-941. 10.1016/j.molcel.2009.11.020.View ArticleGoogle Scholar
  5. Uniacke J, Zerges W: Stress induces the assembly of RNA granules in the chloroplast of Chlamydomonas reinhardtii. J Cell Biol. 2008, 182 (4): 641-646. 10.1083/jcb.200805125.View ArticleGoogle Scholar
  6. Kedersha N, Stoecklin G, Ayodele M, Yacono P, Lykke-Andersen J, Fritzler MJ, Scheuner D, Kaufman RJ, Golan DE, Anderson P: Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol. 2005, 169 (6): 871-884.View ArticleGoogle Scholar
  7. Teixeira D, Sheth U, Valencia-Sanchez MA, Brengues M, Parker R: Processing bodies require RNA for assembly and contain nontranslating mRNAs. Rna. 2005, 11 (4): 371-382. 10.1261/rna.7258505.View ArticleGoogle Scholar
  8. Ling SHM, Qamra R, Song H: Structural and functional insights into eukaryotic mRNA decapping. Wiley Interdisciplinary Reviews: RNA. 2011, 2 (2): 193-10.1002/wrna.44.View ArticleGoogle Scholar
  9. Sheth U, Parker R: Targeting of aberrant mRNAs to cytoplasmic processing bodies. Cell. 2006, 125 (6): 1095-1109. 10.1016/j.cell.2006.04.037.View ArticleGoogle Scholar
  10. Brengues M, Teixeira D, Parker R: Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science. 2005, 310 (5747): 486-489. 10.1126/science.1115791.View ArticleGoogle Scholar
  11. Sheth U, Parker R: Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science. 2003, 300 (5620): 805-808. 10.1126/science.1082320.View ArticleGoogle Scholar
  12. Decker CJ, Teixeira D, Parker R: Edc3p and a glutamine/asparagine-rich domain of Lsm4p function in processing body assembly in Saccharomyces cerevisiae. J Cell Biol. 2007, 179 (3): 437-449. 10.1083/jcb.200704147.View ArticleGoogle Scholar
  13. Reijns MA, Alexander RD, Spiller MP, Beggs JD: A role for Q/N-rich aggregation-prone regions in P-body localization. J Cell Sci. 2008, 121 (Pt 15): 2463-2472.View ArticleGoogle Scholar
  14. Mazzoni C, D'Addario I, Falcone C: The C-terminus of the yeast Lsm4p is required for the association to P-bodies. FEBS Lett. 2007, 581 (25): 4836-4840. 10.1016/j.febslet.2007.09.009.View ArticleGoogle Scholar
  15. Michelitsch MD, Weissman JS: A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions. Proc Natl Acad Sci USA. 2000, 97 (22): 11910-11915. 10.1073/pnas.97.22.11910.View ArticleGoogle Scholar
  16. Brengues M, Parker R: Accumulation of polyadenylated mRNA, Pab1p, eIF4E, and eIF4G with P-bodies in Saccharomyces cerevisiae. Mol Biol Cell. 2007, 18 (7): 2592-2602. 10.1091/mbc.E06-12-1149.View ArticleGoogle Scholar
  17. Hoyle NP, Castelli LM, Campbell SG, Holmes LE, Ashe MP: Stress-dependent relocalization of translationally primed mRNPs to cytoplasmic granules that are kinetically and spatially distinct from P-bodies. J Cell Biol. 2007, 179 (1): 65-74. 10.1083/jcb.200707010.View ArticleGoogle Scholar
  18. Buchan JR, Muhlrad D, Parker R: P bodies promote stress granule assembly in Saccharomyces cerevisiae. J Cell Biol. 2008, 183 (3): 441-455. 10.1083/jcb.200807043.View ArticleGoogle Scholar
  19. Grousl T, Ivanov P, Frydlova I, Vasicova P, Janda F, Vojtova J, Malinska K, Malcova I, Novakova L, Janoskova D, Valasek L, Hasek J: Robust heat shock induces eIF2alpha-phosphorylation-independent assembly of stress granules containing eIF3 and 40S ribosomal subunits in budding yeast, Saccharomyces cerevisiae. J Cell Sci. 2009, 122 (Pt 12): 2078-2088.View ArticleGoogle Scholar
  20. Eulalio A, Behm-Ansmant I, Schweizer D, Izaurralde E: P-body formation is a consequence, not the cause, of RNA-mediated gene silencing. Mol Cell Biol. 2007, 7 (11): 3970-3981.View ArticleGoogle Scholar
  21. Stalder L, Muhlemann O: Processing bodies are not required for mammalian nonsense-mediated mRNA decay. Rna. 2009, 15 (7): 1265-1273. 10.1261/rna.1672509.View ArticleGoogle Scholar
  22. Garcia-Fruitos E: Inclusion bodies: a new concept. Microb Cell Fact. 9: 80-Google Scholar
  23. Peternel S, Komel R: Isolation of biologically active nanomaterial (inclusion bodies) from bacterial cells. Microb Cell Fact. 9: 66-Google Scholar
  24. Rodriguez-Carmona E, Cano-Garrido O, Seras-Franzoso J, Villaverde A, Garcia-Fruitos E: Isolation of cell-free bacterial inclusion bodies. Microb Cell Fact. 9: 71-Google Scholar
  25. An S, Kumar R, Sheets ED, Benkovic SJ: Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science. 2008, 320 (5872): 103-106. 10.1126/science.1152241.View ArticleGoogle Scholar
  26. Narayanaswamy R, Levy M, Tsechansky M, Stovall GM, O'Connell JD, Mirrielees J, Ellington AD, Marcotte EM: Widespread reorganization of metabolic enzymes into reversible assemblies upon nutrient starvation. Proc Natl Acad Sci USA. 2009, 106 (25): 10147-10152. 10.1073/pnas.0812771106.View ArticleGoogle Scholar
  27. Campbell SG, Ashe MP: Localization of the translational guanine nucleotide exchange factor eIF2B: a common theme for GEFs?. Cell Cycle. 2006, 5 (7): 678-680. 10.4161/cc.5.7.2607.View ArticleGoogle Scholar
  28. Campbell SG, Hoyle NP, Ashe MP: Dynamic cycling of eIF2 through a large eIF2B-containing cytoplasmic body: implications for translation control. J Cell Biol. 2005, 170 (6): 925-934. 10.1083/jcb.200503162.View ArticleGoogle Scholar
  29. Liu-Yesucevitz L, Bilgutay A, Zhang YJ, Vanderwyde T, Citro A, Mehta T, Zaarur N, McKee A, Bowser R, Sherman M, Petrucelli L, Wolozin B: Tar DNA binding protein-43 (TDP-43) associates with stress granules: analysis of cultured cells and pathological brain tissue. PLoS One. 2010, 5 (10): e13250-10.1371/journal.pone.0013250.View ArticleGoogle Scholar
  30. Thomas MG, Loschi M, Desbats MA, Boccaccio GL: RNA granules: the good, the bad and the ugly. Cell Signal. 2011, 23 (2): 324-334. 10.1016/j.cellsig.2010.08.011.View ArticleGoogle Scholar
  31. Carrio M, Gonzalez-Montalban N, Vera A, Villaverde A, Ventura S: Amyloid-like properties of bacterial inclusion bodies. J Mol Biol. 2005, 347 (5): 1025-1037. 10.1016/j.jmb.2005.02.030.View ArticleGoogle Scholar
  32. Sabate R, Espargaro A, Saupe SJ, Ventura S: Characterization of the amyloid bacterial inclusion bodies of the HET-s fungal prion. Microb Cell Fact. 2009, 8: 56-10.1186/1475-2859-8-56.View ArticleGoogle Scholar
  33. Vazquez E, Villaverde A: Engineering building blocks for self-assembling protein nanoparticles. Microb Cell Fact. 2010, 9: 101-10.1186/1475-2859-9-101.View ArticleGoogle Scholar
  34. Villaverde A: Nanotechnology, bionanotechnology and microbial cell factories. Microb Cell Fact. 2010, 9: 53-10.1186/1475-2859-9-53.View ArticleGoogle Scholar


© Giménez-Barcons and Díez; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.