Biology:P-bodies
In cellular biology, P-bodies, or processing bodies, are distinct foci formed by phase separation within the cytoplasm of a eukaryotic cell consisting of many enzymes involved in mRNA turnover.[1] P-bodies are highly conserved structures and 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 (miRNA) induced mRNA silencing.[2] 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.[3][4] Purification and sequencing of the mRNA from purified processing bodies showed that these mRNAs are largely translationally repressed upstream of translation initiation and are protected from 5' mRNA decay.[5]
P-bodies were originally proposed to be the sites of mRNA degradation in the cell and involved in decapping and digestion of mRNAs earmarked for destruction.[6][7] Later work called this into question suggesting P bodies store mRNA until needed for translation.[8][5][9]
In neurons, P-bodies are moved by motor proteins in response to stimulation. This is likely tied to local translation in dendrites.[10]
History
P-bodies were first described in the scientific literature by Bashkirov et al.[11] 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.[12][13][14], when researchers demonstrated that multiple proteins involved with mRNA degradation localize to the foci. Their importance was recognized after experimental evidence was obtained pointing to P-bodies as the sites of mRNA degradation in the cell.[7] The researchers named these structures processing bodies or "P bodies". During this time, many descriptive names were used also 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.[7] Recently evidence has been presented suggesting that GW-bodies and P-bodies may in fact be different cellular components.[15] 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 and they contain largely non-overlapping proteins.[5] 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.[16]
Associations with 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).[2][17][18][19][20] 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.
Protein composition
In 2017, a new method to purify processing bodies was published.[5] Hubstenberger et al. used fluorescence-activated particle sorting (a method based on the ideas of fluorescence-activated cell sorting) to purify processing bodies from human epithelial cells. From these purified processing bodies they were able to use mass spectrometry and RNA sequencing to determine which proteins and RNAs are found in processing bodies, respectively. This study identified 125 proteins that are significantly associated with processing bodies.[5] Notably this work provided the most compelling evidence up to this date that P-bodies might not be the sites of degradation in the cell and instead used for storage of translationally repressed mRNA. This observation was further supported by single molecule imaging of mRNA by the Chao group in 2017.[21]
In 2018, Youn et al. took a proximity labeling approach called BioID to identify and predict the processing body proteome.[22] They engineered cells to express several processing body-localized proteins as fusion proteins with the BirA* enzyme. When the cells are incubated with biotin, BirA* will biotinylate proteins that are nearby, thus tagging the proteins within processing bodies with a biotin tag. Streptavidin was then used to isolate the tagged proteins and mass spectrometry to identify them. Using this approach, Youn et al. identified 42 proteins that localize to processing bodies.[22]
Gene ID | Protein | References | Also found in stress granules? |
---|---|---|---|
MOV10 | MOV10 | [5][22] | Yes |
EDC3 | EDC3 | [22] | Yes |
EDC4 | EDC4 | [5] | Yes |
ZCCHC11 | TUT4 | [5] | No |
DHX9 | DHX9 | [5] | No |
RPS27A | RS27A | [5] | No |
UPF1 | RENT1 | [5] | Yes |
ZCCHC3 | ZCHC3 | [5] | No |
SMARCA5 | SMCA5 | [5] | No |
TOP2A | TOP2A | [5] | No |
HSPA2 | HSP72 | [5] | No |
SPTAN1 | SPTN1 | [5] | No |
SMC1A | SMC1A | [5] | No |
ACTBL2 | ACTBL | [5] | Yes |
SPTBN1 | SPTB2 | [5] | No |
DHX15 | DHX15 | [5] | No |
ARG1 | ARGI1 | [5] | No |
TOP2B | TOP2B | [5] | No |
APOBEC3F | ABC3F | [5] | No |
NOP58 | NOP58 | [5] | Yes |
RPF2 | RPF2 | [5] | No |
S100A9 | S100A9 | [5] | Yes |
DDX41 | DDX41 | [5] | No |
KIF23 | KIF23 | [5] | Yes |
AZGP1 | ZA2G | [5] | No |
DDX50 | DDX50 | [5] | Yes |
SERPINB3 | SPB3 | [5] | No |
SBSN | SBSN | [5] | No |
BAZ1B | BAZ1B | [5] | No |
MYO1C | MYO1C | [5] | No |
EIF4A3 | IF4A3 | [5] | No |
SERPINB12 | SPB12 | [5] | No |
EFTUD2 | U5S1 | [5] | No |
RBM15B | RB15B | [5] | No |
AGO2 | AGO2 | [5] | Yes |
MYH10 | MYH10 | [5] | No |
DDX10 | DDX10 | [5] | No |
FABP5 | FABP5 | [5] | No |
SLC25A5 | ADT2 | [5] | No |
DMKN | DMKN | [5] | No |
DCP2 | DCP2 | No | |
S100A8 | S10A8 | [5] | No |
NCBP1 | NCBP1 | [5] | No |
YTHDC2 | YTDC2 | [5] | No |
NOL6 | NOL6 | [5] | No |
XAB2 | SYF1 | [5] | No |
PUF60 | PUF60 | [5] | No |
RBM19 | RBM19 | [5] | No |
WDR33 | WDR33 | [5] | No |
PNRC1 | PNRC1 | [5] | No |
SLC25A6 | ADT3 | [5] | No |
MCM7 | MCM7 | [5] | Yes |
GSDMA | GSDMA | [5] | No |
HSPB1 | HSPB1 | [5] | Yes |
LYZ | LYSC | [5] | No |
DHX30 | DHX30 | [5] | Yes |
BRIX1 | BRX1 | [5] | No |
MEX3A | MEX3A | [5] | Yes |
MSI1 | MSI1H | [5] | Yes |
RBM25 | RBM25 | [5] | No |
UTP11L | UTP11 | [5] | No |
UTP15 | UTP15 | [5] | No |
SMG7 | SMG7 | [5][22] | Yes |
AGO1 | AGO1 | [5] | Yes |
LGALS7 | LEG7 | [5] | No |
MYO1D | MYO1D | [5] | No |
XRCC5 | XRCC5 | [5] | No |
DDX6 | DDX6/p54/RCK | [5][22][23][24] | Yes |
ZC3HAV1 | ZCCHV | [5] | Yes |
DDX27 | DDX27 | [5] | No |
NUMA1 | NUMA1 | [5] | No |
DSG1 | DSG1 | [5] | No |
NOP56 | NOP56 | [5] | No |
LSM14B | LS14B | [5] | Yes |
EIF4E2 | EIF4E2 | [22] | Yes |
EIF4ENIF1 | 4ET | [5][22] | Yes |
LSM14A | LS14A | [5][22] | Yes |
IGF2BP2 | IF2B2 | [5] | Yes |
DDX21 | DDX21 | [5] | Yes |
DSC1 | DSC1 | [5] | No |
NKRF | NKRF | [5] | No |
DCP1B | DCP1B | [5][24] | No |
SMC3 | SMC3 | [5] | No |
RPS3 | RS3 | [5] | Yes |
PUM1 | PUM1 | [5] | Yes |
PIP | PIP | [5] | No |
RPL26 | RL26 | [5] | No |
GTPBP4 | NOG1 | [5] | No |
PES1 | PESC | [5] | No |
DCP1A | DCP1A | [5][13][14][25][26] | No |
ELAVL2 | ELAV2 | [5] | Yes |
IGLC2 | LAC2 | [5] | No |
IGF2BP1 | IF2B1 | [5] | Yes |
RPS16 | RS16 | [5] | No |
HNRNPU | HNRPU | [5] | No |
IGF2BP3 | IF2B3 | [5] | Yes |
SF3B1 | SF3B1 | [5] | No |
STAU2 | STAU2 | [5] | Yes |
ZFR | ZFR | [5] | No |
HNRNPM | HNRPM | [5] | No |
ELAVL1 | ELAV1 | [5] | Yes |
FAM120A | F120A | [5] | Yes |
STRBP | STRBP | [5] | No |
RBM15 | RBM15 | [5] | No |
LMNB2 | LMNB2 | [5] | No |
NIFK | MK67I | [5] | No |
TF | TRFE | [5] | No |
HNRNPR | HNRPR | [5] | No |
LMNB1 | LMNB1 | [5] | No |
ILF2 | ILF2 | [5] | No |
H2AFY | H2AY | [5] | No |
RBM28 | RBM28 | [5] | No |
MATR3 | MATR3 | [5] | No |
SYNCRIP | HNRPQ | [5] | Yes |
HNRNPCL1 | HNRCL | [5] | No |
APOA1 | APOA1 | [5] | No |
XRCC6 | XRCC6 | [5] | No |
RPS4X | RS4X | [5] | No |
DDX18 | DDX18 | [5] | No |
ILF3 | ILF3 | [5] | Yes |
SAFB2 | SAFB2 | [5] | Yes |
RBMX | RBMX | [5] | No |
ATAD3A | ATD3A | [5] | Yes |
HNRNPC | HNRPC | [5] | No |
RBMXL1 | RMXL1 | [5] | No |
IMMT | IMMT | [5] | No |
ALB | ALBU | [5] | No |
CSNK1D | CK1𝛿 | [23] | No |
XRN1 | XRN1 | [11][13][22][25] | Yes |
TNRC6A | GW182 | [22][25][27][26][28] | Yes |
TNRC6B | TNRC6B | [22] | Yes |
TNRC6C | TNRC6C | [22] | Yes |
LSM4 | LSM4 | [26][13] | No |
LSM1 | LSM1 | [13] | No |
LSM2 | LSM2 | [13] | No |
LSM3 | LSM3 | [13][24] | Yes |
LSM5 | LSM5 | [13] | No |
LSM6 | LSM6 | [13] | No |
LSM7 | LSM7 | [13] | No |
CNOT1 | CCR4/CNOT1 | [24][22] | Yes |
CNOT10 | CNOT10 | [22] | Yes |
CNOT11 | CNOT11 | [22] | Yes |
CNOT2 | CNOT2 | [22] | Yes |
CNOT3 | CNOT3 | [22] | Yes |
CNOT4 | CNOT4 | [22] | Yes |
CNOT6 | CNOT6 | [22] | Yes |
CNOT6L | CNOT6L | [22] | Yes |
CNOT7 | CNOT7 | [22] | Yes |
CNOT8 | CNOT8 | [22] | Yes |
CNOT9 | CNOT9 | [22] | No |
RBFOX1 | RBFOX1 | [29] | Yes |
ANKHD1 | ANKHD1 | [22] | Yes |
ANKRD17 | ANKRD17 | [22] | Yes |
BTG3 | BTG3 | [22] | Yes |
CEP192 | CEP192 | [22] | No |
CPEB4 | CPEB4 | [22] | Yes |
CPVL | CPVL | [22] | Yes |
DIS3L | DIS3L | [22] | No |
DVL3 | DVL3 | [22] | No |
FAM193A | FAM193A | [22] | No |
GIGYF2 | GIGYF2 | [22] | Yes |
HELZ | HELZ | [22] | Yes |
KIAA0232 | KIAA0232 | [22] | Yes |
KIAA0355 | KIAA0355 | [22] | No |
MARF1 | MARF1 | [22] | Yes |
N4BP2 | N4BP2 | [22] | No |
PATL1 | PATL1 | [22] | Yes |
RNF219 | RNF219 | [22] | Yes |
ST7 | ST7 | [22] | Yes |
TMEM131 | TMEM131 | [22] | Yes |
TNKS1BP1 | TNKS1BP1 | [22] | Yes |
TTC17 | TTC17 | [22] | Yes |
References
- ↑ "P-Bodies: Composition, Properties, and Functions". Biochemistry 57 (17): 2424–2431. May 2018. doi:10.1021/acs.biochem.7b01162. PMID 29381060.
- ↑ Jump up to: 2.0 2.1 "On track with P-bodies". Biochemical Society Transactions 38 (Pt 1): 242–251. February 2010. doi:10.1042/BST0380242. PMID 20074068.
- ↑ "Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies". Science 310 (5747): 486–489. October 2005. doi:10.1126/science.1115791. PMID 16141371. Bibcode: 2005Sci...310..486B.
- ↑ "Relief of microRNA-mediated translational repression in human cells subjected to stress". Cell 125 (6): 1111–1124. June 2006. doi:10.1016/j.cell.2006.04.031. PMID 16777601.
- ↑ Jump up to: 5.000 5.001 5.002 5.003 5.004 5.005 5.006 5.007 5.008 5.009 5.010 5.011 5.012 5.013 5.014 5.015 5.016 5.017 5.018 5.019 5.020 5.021 5.022 5.023 5.024 5.025 5.026 5.027 5.028 5.029 5.030 5.031 5.032 5.033 5.034 5.035 5.036 5.037 5.038 5.039 5.040 5.041 5.042 5.043 5.044 5.045 5.046 5.047 5.048 5.049 5.050 5.051 5.052 5.053 5.054 5.055 5.056 5.057 5.058 5.059 5.060 5.061 5.062 5.063 5.064 5.065 5.066 5.067 5.068 5.069 5.070 5.071 5.072 5.073 5.074 5.075 5.076 5.077 5.078 5.079 5.080 5.081 5.082 5.083 5.084 5.085 5.086 5.087 5.088 5.089 5.090 5.091 5.092 5.093 5.094 5.095 5.096 5.097 5.098 5.099 5.100 5.101 5.102 5.103 5.104 5.105 5.106 5.107 5.108 5.109 5.110 5.111 5.112 5.113 5.114 5.115 5.116 5.117 5.118 5.119 5.120 5.121 5.122 5.123 5.124 5.125 5.126 5.127 5.128 "P-Body Purification Reveals the Condensation of Repressed mRNA Regulons". Molecular Cell 68 (1): 144–157.e5. October 2017. doi:10.1016/j.molcel.2017.09.003. PMID 28965817.
- ↑ Long, Roy M.; McNally, Mark T. (2003-05-01). "mRNA Decay: X (XRN1) Marks the Spot" (in English). Molecular Cell 11 (5): 1126–1128. doi:10.1016/S1097-2765(03)00198-9. ISSN 1097-2765. https://www.cell.com/molecular-cell/abstract/S1097-2765(03)00198-9.
- ↑ Jump up to: 7.0 7.1 7.2 "Decapping and decay of messenger RNA occur in cytoplasmic processing bodies". Science 300 (5620): 805–808. May 2003. doi:10.1126/science.1082320. PMID 12730603. Bibcode: 2003Sci...300..805S.
- ↑ Brengues, Muriel; Teixeira, Daniela; Parker, Roy (2005-10-21). "Movement of Eukaryotic mRNAs Between Polysomes and Cytoplasmic Processing Bodies" (in en). Science 310 (5747): 486–489. doi:10.1126/science.1115791. ISSN 0036-8075. PMID 16141371. PMC 1863069. https://www.science.org/doi/10.1126/science.1115791.
- ↑ Horvathova, Ivana; Voigt, Franka; Kotrys, Anna V.; Zhan, Yinxiu; Artus-Revel, Caroline G.; Eglinger, Jan; Stadler, Michael B.; Giorgetti, Luca et al. (2017-11-02). "The Dynamics of mRNA Turnover Revealed by Single-Molecule Imaging in Single Cells" (in English). Molecular Cell 68 (3): 615–625.e9. doi:10.1016/j.molcel.2017.09.030. ISSN 1097-2765. PMID 29056324. https://www.cell.com/molecular-cell/abstract/S1097-2765(17)30708-6.
- ↑ "Dendrites of mammalian neurons contain specialized P-body-like structures that respond to neuronal activation". The Journal of Neuroscience 28 (51): 13793–13804. December 2008. doi:10.1523/JNEUROSCI.4155-08.2008. PMID 19091970.
- ↑ Jump up to: 11.0 11.1 "A mouse cytoplasmic exoribonuclease (mXRN1p) with preference for G4 tetraplex substrates". The Journal of Cell Biology 136 (4): 761–773. February 1997. doi:10.1083/jcb.136.4.761. PMID 9049243.
- ↑ "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. April 2002. doi:10.1091/mbc.01-11-0544. PMID 11950943.
- ↑ Jump up to: 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 13.9 "The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci". RNA 8 (12): 1489–1501. December 2002. doi:10.1017/S1355838202021726. PMID 12515382.
- ↑ Jump up to: 14.0 14.1 "Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures". The EMBO Journal 21 (24): 6915–6924. December 2002. doi:10.1093/emboj/cdf678. PMID 12486012.
- ↑ "Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity". Nature Cell Biology 11 (9): 1143–1149. September 2009. doi:10.1038/ncb1929. PMID 19684575.
- ↑ "Stress-dependent relocalization of translationally primed mRNPs to cytoplasmic granules that are kinetically and spatially distinct from P-bodies". The Journal of Cell Biology 179 (1): 65–74. October 2007. doi:10.1083/jcb.200707010. PMID 17908917.
- ↑ "MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies". Nature Cell Biology 7 (7): 719–723. July 2005. doi:10.1038/ncb1274. PMID 15937477.
- ↑ "A role for the P-body component GW182 in microRNA function". Nature Cell Biology 7 (12): 1261–1266. December 2005. doi:10.1038/ncb1333. PMID 16284623.
- ↑ "Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies". Nature Cell Biology 7 (6): 633–636. June 2005. doi:10.1038/ncb1265. PMID 15908945.
- ↑ "The GW182 protein colocalizes with mRNA degradation associated proteins hDcp1 and hLSm4 in cytoplasmic GW bodies". RNA 9 (10): 1171–1173. October 2003. doi:10.1261/rna.5810203. PMID 13130130.
- ↑ Horvathova, Ivana; Voigt, Franka; Kotrys, Anna V.; Zhan, Yinxiu; Artus-Revel, Caroline G.; Eglinger, Jan; Stadler, Michael B.; Giorgetti, Luca et al. (2017-11-02). "The Dynamics of mRNA Turnover Revealed by Single-Molecule Imaging in Single Cells" (in English). Molecular Cell 68 (3): 615–625.e9. doi:10.1016/j.molcel.2017.09.030. ISSN 1097-2765. PMID 29056324. https://www.cell.com/molecular-cell/abstract/S1097-2765(17)30708-6.
- ↑ Jump up to: 22.00 22.01 22.02 22.03 22.04 22.05 22.06 22.07 22.08 22.09 22.10 22.11 22.12 22.13 22.14 22.15 22.16 22.17 22.18 22.19 22.20 22.21 22.22 22.23 22.24 22.25 22.26 22.27 22.28 22.29 22.30 22.31 22.32 22.33 22.34 22.35 22.36 22.37 22.38 22.39 22.40 22.41 22.42 22.43 22.44 "High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies". Molecular Cell 69 (3): 517–532.e11. February 2018. doi:10.1016/j.molcel.2017.12.020. PMID 29395067.
- ↑ Jump up to: 23.0 23.1 "The Activity-Dependent Regulation of Protein Kinase Stability by the Localization to P-Bodies". Genetics 203 (3): 1191–1202. July 2016. doi:10.1534/genetics.116.187419. PMID 27182950.
- ↑ Jump up to: 24.0 24.1 24.2 24.3 "Cytoplasmic foci are sites of mRNA decay in human cells". The Journal of Cell Biology 165 (1): 31–40. April 2004. doi:10.1083/jcb.200309008. PMID 15067023.
- ↑ Jump up to: 25.0 25.1 25.2 Cite error: Invalid
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tag; no text was provided for refs namedKedersha_2005
- ↑ Jump up to: 26.0 26.1 26.2 "The GW182 protein colocalizes with mRNA degradation associated proteins hDcp1 and hLSm4 in cytoplasmic GW bodies". RNA 9 (10): 1171–1173. October 2003. doi:10.1261/rna.5810203. PMID 13130130.
- ↑ "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. April 2002. doi:10.1091/mbc.01-11-0544. PMID 11950943.
- ↑ "GW182 is critical for the stability of GW bodies expressed during the cell cycle and cell proliferation". Journal of Cell Science 117 (Pt 23): 5567–5578. November 2004. doi:10.1242/jcs.01477. PMID 15494374.
- ↑ "Stress-dependent miR-980 regulation of Rbfox1/A2bp1 promotes ribonucleoprotein granule formation and cell survival". Nature Communications 9 (1): 312. January 2018. doi:10.1038/s41467-017-02757-w. PMID 29358748. Bibcode: 2018NatCo...9..312K.
Further reading
- "On track with P-bodies". Biochemical Society Transactions 38 (Pt 1): 242–251. February 2010. doi:10.1042/BST0380242. PMID 20074068.
- "P bodies: at the crossroads of post-transcriptional pathways". Nature Reviews. Molecular Cell Biology 8 (1): 9–22. January 2007. doi:10.1038/nrm2080. PMID 17183357.
- "Molecular biology. P-bodies mark the spot for controlling protein production". Science 310 (5749): 764–765. November 2005. doi:10.1126/science.310.5749.764. PMID 16272094.
- "RNA granules: post-transcriptional and epigenetic modulators of gene expression". Nature Reviews. Molecular Cell Biology 10 (6): 430–436. June 2009. doi:10.1038/nrm2694. PMID 19461665.
Original source: https://en.wikipedia.org/wiki/P-bodies.
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