P-bodies

Not to be confused with P element.
"P-body" redirects here. For the fictional robot, see Portal 2.

Processing bodies (P-bodies) are distinct foci within the cytoplasm of the eukaryotic cell consisting of many enzymes involved in mRNA turnover. P-bodies have been observed in somatic cells originating from vertebrates and invertebrates, plants and yeast. To date, P-bodies have been demonstrated to play fundamental roles in general mRNA decay, nonsense-mediated mRNA decay, adenylate-uridylate-rich element mediated mRNA decay, and microRNA induced mRNA silencing.[1] Not all mRNAs which enter P-bodies are degraded, as it has been demonstrated that some mRNAs can exit P-bodies and re-initiate translation.[2][3]

The following activities have been demonstrated to occur in or to be associated with P-bodies:

In neurons, P-bodies move by motor proteins in response to stimulation. This is likely tied to local translation in dendrites.[4]

P-bodies were first described in the scientific literature by Bashkirov et al.[5] in 1997, in which they describe "small granules… discrete, prominent foci" as the cytoplasmic location of the mouse exoribonuclease mXrn1p. It wasn’t until 2002 that a glimpse into the nature and importance of these cytoplasmic foci was published.[6][7][8] In 2002, researchers demonstrated that multiple proteins involved with mRNA degradation localize to the foci. During this time, many descriptive names were used to identify the processing bodies, including "GW-bodies" and "decapping-bodies"; however "P-bodies" was the term chosen and is now widely used and accepted in the scientific literature. Recently evidence has been presented suggesting that GW-bodies and P-bodies may in fact be different cellular components.[9] The evidence being that GW182 and Ago2, both associated with miRNA gene silencing, are found exclusively in multivesicular bodies or GW-bodies and are not localized to P-bodies. Also of note, P-bodies are not equivalent to stress granules, the two structures support overlapping cellular functions but generally occur under different stimuli. Hoyle et al. suggests a novel site termed EGP bodies, or stress granules, may be responsible for mRNA storage as these sites lack the decapping enzyme.[10]

P-bodies and microRNA

microRNA mediated repression occurs in two ways, either by translational repression or stimulating mRNA decay. miRNA recruit the RISC complex to the mRNA to which they are bound. The link to P-bodies comes by the fact that many, if not most, of the proteins necessary for miRNA gene silencing are localized to P-bodies, as reviewed by Kulkarni et al. (2010).[1][11][12][13][14] These proteins include, but are not limited to, the scaffold protein GW182, Argonaute (Ago), decapping enzymes and RNA helicases. The current evidence points toward P-bodies as being scaffolding centers of miRNA function, especially due to the evidence that a knock down of GW182 disrupts P-body formation. However, there remain many unanswered questions about P-bodies and their relationship to miRNA activity. Specifically, it is unknown whether there is a context dependent (stress state versus normal) specificity to the P-body's mechanism of action. Based on the evidence that P-bodies sometimes are the site of mRNA decay and sometimes the mRNA can exit the P-bodies and re-initiate translation, the question remains of what controls this switch. Another ambiguous point to be addressed is whether the proteins that localize to P-bodies are actively functioning in the miRNA gene silencing process or whether they are merely on standby.

References

  1. 1 2 Kulkarni, M.; Ozgur, S.; Stoecklin, G. (2010). "On track with P-bodies". Biochemical Society Transactions. 38 (Pt 1): 242–251. doi:10.1042/BST0380242. PMID 20074068.
  2. ↑ Brengues, M.; Teixeira, D.; Parker, R. (2005). "Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies". Science. 310 (5747): 486–489. Bibcode:2005Sci...310..486B. doi:10.1126/science.1115791. PMC 1863069Freely accessible. PMID 16141371.
  3. ↑ Bhattacharyya, S.; Habermacher, R.; Martine, U.; Closs, E.; Filipowicz, W. (2006). "Relief of microRNA-mediated translational repression in human cells subjected to stress". Cell. 125 (6): 1111–1124. doi:10.1016/j.cell.2006.04.031. PMID 16777601.
  4. ↑ Cougot, Nicolas; Bhattacharyya, Suvendra N.; Tapia-arancibia, Lucie; Bordonne, Remy; Filipowicz, Witold; Bertrand, Edouard; Rage, Florence (2008). "Dendrites of Mammalian Neurons Contain Specialized P-Body-Like Structures That Respond to Neuronal Activation". Journal of Neuroscience. 28 (51): 13793–804. doi:10.1523/JNEUROSCI.4155-08.2008. PMID 19091970.
  5. ↑ Bashkirov, V. I.; Scherthan, H.; Solinger, J. A.; Buerstedde, J. -M.; Heyer, W. -D. (1997). "A Mouse Cytoplasmic Exoribonuclease (mXRN1p) with Preference for G4 Tetraplex Substrates". Journal of Cell Biology. 136 (4): 761–73. doi:10.1083/jcb.136.4.761. PMC 2132493Freely accessible. PMID 9049243.
  6. ↑ Eystathioy, T.; Chan, E.; Tenenbaum, S.; Keene, J.; Griffith, K.; Fritzler, M. (2002). "A phosphorylated cytoplasmic autoantigen, GW182, associates with a unique population of human mRNAs within novel cytoplasmic speckles". Molecular Biology of the Cell. 13 (4): 1338–1351. doi:10.1091/mbc.01-11-0544. PMC 102273Freely accessible. PMID 11950943.
  7. ↑ Ingelfinger, D.; Arndt-Jovin, D. J.; Lührmann, R.; Achsel, T. (2002). "The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci". RNA. 8 (12): 1489–1501. doi:10.1017/S1355838202021726. PMC 1370355Freely accessible. PMID 12515382.
  8. ↑ Van Dijk, E.; Cougot, N.; Meyer, S.; Babajko, S.; Wahle, E.; Séraphin, B. (2002). "Human Dcp2: A catalytically active mRNA decapping enzyme located in specific cytoplasmic structures". The EMBO Journal. 21 (24): 6915–6924. doi:10.1093/emboj/cdf678. PMC 139098Freely accessible. PMID 12486012.
  9. ↑ Gibbings, D.; Ciaudo, C.; Erhardt, M.; Voinnet, O. (2009). "Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity". Nature Cell Biology. 11 (9): 1143–1149. doi:10.1038/ncb1929. PMID 19684575.
  10. ↑ Hoyle, N.; Castelli, L.; Campbell, S.; Holmes, L.; Ashe, M. (2007). "Stress-dependent relocalization of translationally primed mRNPs to cytoplasmic granules that are kinetically and spatially distinct from P-bodies". Journal of Cell Biology. 179 (1): 65–74. doi:10.1083/jcb.200707010. PMC 2064737Freely accessible. PMID 17908917.
  11. ↑ Liu, J.; Valencia-Sanchez, M.; Hannon, G.; Parker, R. (2005). "MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies". Nature Cell Biology. 7 (7): 719–723. doi:10.1038/ncb1274. PMC 1855297Freely accessible. PMID 15937477.
  12. ↑ Liu, J.; Rivas, F.; Wohlschlegel, J.; Yates Jr, 3.; Parker, R.; Hannon, G. (2005). "A role for the P-body component GW182 in microRNA function". Nature Cell Biology. 7 (12): 1261–1266. doi:10.1038/ncb1333. PMC 1804202Freely accessible. PMID 16284623.
  13. ↑ Sen, G.; Blau, H. (2005). "Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies". Nature Cell Biology. 7 (6): 633–636. doi:10.1038/ncb1265. PMID 15908945.
  14. ↑ Eystathioy, T.; Jakymiw, A.; Chan, E. K.; Séraphin, B.; Cougot, N.; Fritzler, M. J. (2003). "The GW182 protein colocalizes with mRNA degradation associated proteins hDcp1 and hLSm4 in cytoplasmic GW bodies". RNA. 9 (10): 1171–1173. doi:10.1261/rna.5810203. PMC 1370480Freely accessible. PMID 13130130.

Further reading

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