P-bodies (PBs) are cytosolic biomolecular condensates that form by the phase separation of the translationally-arrested mRNAs and proteins at specific locations in the cytoplasm, in response to environmental stress. This way, P-bodies play a major role in controlling translation and buffering the proteome. Enzymes involved in mRNA processing were the first proteins found in these ribonucleoprotein (RNP) complexes. The principal 5'-to-3' exonuclease, Xrn1, and the Dcp1 and Dcp2 components of the major mRNA decapping complex are among these members. Therefore, P-bodies were first considered to be active mRNA degradation sites. However, recent research suggests that the major role of P-body granules may not be mRNA turnover. Yeast and mammalian cells that were deficient for P-body formation, for example, had no major problems in mRNA degradation. It is now known that mRNAs in P-bodies are translationally repressed, but not decayed, which can shift back to the cytosol and re-enter translation. Furthermore, several studies have shown that certain mRNAs are stored within these granules for a long time (28965817, 31626750, 31317215, 31591142,32873715).
Formation, Composition & dynamics (Assembly and disassembly)
Relation to human diseases
Proteome
Formation, Composition & Dynamics of (Assembly and disassembly)
PBs are assemblies of untranslating mRNA complexes with RNA decay machinery components. P-bodies continuously exist in the cytoplasm, but tend to enlarge during stress. In comparison, stress granules (SGs) only form or are visible in the cytoplasm during stress, even though SGs also contain nontranslating RNAs (31591142). Although recent investigations demonstrate substantially greater protein similarity amongst SGs and PBs, PBs are particularly enriched with components involved in mRNA degradation and decay. Despite having a thorough understanding of their composition and behavior, the function of these granules is still a mystery (32873715).
Using an RNA-mediated interference-based screen, 18794846 found 39 genes required for PB assembly, and several genes which coordinate their assembly.
32873715 shows components of assembly and disassembly of PBs.
Related human diseases
The phase separation of RNA and associated proteins into microscopically visible cytosolic or nuclear structures is an important mediator of dynamic compartmentalization, and changes in the dynamics of these RNA-associated structures underpin the pathology of several neurodegenerative disorders.
While direct evidence for the significance of PBs in disease is still scarce, current research on the compositional enrichment of mRNAs contained inside this organelle suggests that PBs play a vital regulatory role in chromatin regulation, RNA processing, protein synthesis, and protein breakdown. Furthermore, some PB protein components control the translation or stability of transcripts implicated in the inflammatory response directly (31626750).
32873715 describes PBs in the context of several diseases.
Proteome
28965817 developed a fluorescence-activated particle sorting (FAPS) method to purify cytosolic processing bodies (P-bodies) from human epithelial cells. This study identified hundreds of proteins and thousands of mRNAs which form a dense network of connections distinguishing PB RNPs from non-PB RNPs. It is shown here that mRNAs segregating into PBs are translationally repressed, but not decayed. The study claims this repression as an explanation for the poor genome-wide correlation between RNA and protein abundance.
31626750 created an RNA granule database (RNAgranuleDB), which is available at http://rnagranuledb. lunenfeld.ca. Through this website, users can find an updated and manually curated matrix of evidence from the primary literature supporting whether a protein resides in SGs or PBs, alongside a cumulative confidence score and protein feature analysis. This provides a comprehensive summary of SG and PB components.
30082464, 31591142provide useful insight comparing SG and PB in transcriptome and translational control.
References
Hubstenberger A, Courel M, Bénard M, Souquere S, Ernoult-Lange M, Chouaib R, Yi Z, Morlot JB, Munier A, Fradet M, Daunesse M, Bertrand E, Pierron G, Mozziconacci J, Kress M, Weil D. P-Body Purification Reveals the Condensation of Repressed mRNA Regulons. Mol Cell. 2017 Oct 5;68(1):144-157.e5. doi: 10.1016/j.molcel.2017.09.003. Epub 2017 Sep 28. PMID: 28965817.
Youn JY, Dyakov BJA, Zhang J, Knight JDR, Vernon RM, Forman-Kay JD, Gingras AC. Properties of Stress Granule and P-Body Proteomes. Mol Cell. 2019 Oct 17;76(2):286-294. doi: 10.1016/j.molcel.2019.09.014. PMID: 31626750.
Zhang B, Herman PK. It is all about the process(ing): P-body granules and the regulation of signal transduction. Curr Genet. 2020 Feb;66(1):73-77. doi: 10.1007/s00294-019-01016-3. Epub 2019 Jul 17. PMID: 31317215; PMCID: PMC6980427.
Matheny T, Rao BS, Parker R. Transcriptome-Wide Comparison of Stress Granules and P-Bodies Reveals that Translation Plays a Major Role in RNA Partitioning. Mol Cell Biol. 2019 Nov 25;39(24):e00313-19. doi: 10.1128/MCB.00313-19. PMID: 31591142; PMCID: PMC6879202.
Riggs CL, Kedersha N, Ivanov P, Anderson P. Mammalian stress granules and P bodies at a glance. J Cell Sci. 2020 Sep 1;133(16):jcs242487. doi: 10.1242/jcs.242487. PMID: 32873715.
Matheny T, Rao BS, Parker R. Transcriptome-Wide Comparison of Stress Granules and P-Bodies Reveals that Translation Plays a Major Role in RNA Partitioning. Mol Cell Biol. 2019 Nov 25;39(24):e00313-19. doi: 10.1128/MCB.00313-19. PMID: 31591142; PMCID: PMC6879202.
Riggs CL, Kedersha N, Ivanov P, Anderson P. Mammalian stress granules and P bodies at a glance. J Cell Sci. 2020 Sep 1;133(16):jcs242487. doi: 10.1242/jcs.242487. PMID: 32873715.
Ohn T, Kedersha N, Hickman T, Tisdale S, Anderson P. A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly. Nat Cell Biol. 2008 Oct;10(10):1224-31. doi: 10.1038/ncb1783. Epub 2008 Sep 14. PMID: 18794846; PMCID: PMC4318256.
Ivanov P, Kedersha N, Anderson P. Stress Granules and Processing Bodies in Translational Control. Cold Spring Harb Perspect Biol. 2019 May 1;11(5):a032813. doi: 10.1101/cshperspect.a032813. PMID: 30082464; PMCID: PMC6496347.