P-bodies
In
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.
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.
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 | [5][13][14][23] | 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][24][25] | 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][25] | 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][23][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 | [24] | No |
XRN1 | XRN1 | [11][13][22][23] | Yes |
TNRC6A | GW182 | [22][23][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][25] | Yes |
LSM5 | LSM5 | [13] | No |
LSM6 | LSM6 | [13] | No |
LSM7 | LSM7 | [13] | No |
CNOT1 | CCR4/CNOT1 | [25][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
- PMID 29381060.
- ^ PMID 20074068.
- PMID 16141371.
- S2CID 18353167.
- ^ PMID 28965817.
- ISSN 1097-2765.
- ^ PMID 12730603.
- PMID 16141371.
- PMID 29056324.
- PMID 19091970.
- ^ PMID 9049243.
- PMID 11950943.
- ^ PMID 12515382.
- ^ PMID 12486012.
- S2CID 205286867.
- PMID 17908917.
- PMID 15937477.
- PMID 16284623.
- S2CID 6085169.
- PMID 13130130.
- PMID 29056324.
- ^ PMID 29395067.
- ^ PMID 15967811.
- ^ PMID 27182950.
- ^ PMID 15067023.
- ^ PMID 13130130.
- PMID 11950943.
- PMID 15494374.
- PMID 29358748.
Further reading
- Kulkarni M, Ozgur S, Stoecklin G (February 2010). "On track with P-bodies". Biochemical Society Transactions. 38 (Pt 1): 242–251. PMID 20074068.
- Eulalio A, Behm-Ansmant I, Izaurralde E (January 2007). "P bodies: at the crossroads of post-transcriptional pathways". Nature Reviews. Molecular Cell Biology. 8 (1): 9–22. S2CID 41419388.
- Marx J (November 2005). "Molecular biology. P-bodies mark the spot for controlling protein production". Science. 310 (5749): 764–765. S2CID 11106208.
- Anderson P, Kedersha N (June 2009). "RNA granules: post-transcriptional and epigenetic modulators of gene expression". Nature Reviews. Molecular Cell Biology. 10 (6): 430–436. S2CID 26578027.