Stress granule
In cellular biology, stress granules are biomolecular condensates in the cytosol composed of proteins and RNA that assemble into 0.1–2 μm membraneless organelles when the cell is under stress. The mRNA molecules found in stress granules are stalled translation pre-initiation complexes associated with 40S ribosomal subunits, translation initiation factors, poly+ mRNA and RNA-binding proteins. While they are membraneless organelles, stress granules have been proposed to be associated with the endoplasmatic reticulum. There are also nuclear stress granules. This article is about the cytosolic variety.
Proposed functions
The function of stress granules remains largely unknown. Stress granules have long been proposed to have a function to protect RNA from harmful conditions, thus their appearance under stress. The accumulation of RNA into dense globules could keep them from reacting with harmful chemicals and safeguard the information coded in their RNA sequence.Stress granules might also function as a decision point for untranslated mRNA. Molecules can go down one of three paths: further storage, degradation, or re-initiation of translation. Conversely, it has also been argued that stress granules are not important sites for mRNA storage nor do they serve as an intermediate location for mRNA in transit between a state of storage and a state of degradation.
Efforts to identify all RNA within stress granules in an unbiased way by sequencing RNA from biochemically purified stress granule "cores" have shown that RNA are not recruited to stress granules in a sequence-specific manner, but rather generically, with longer and/or less-optimally translated transcripts being enriched. These data imply that the stress granule transcriptome is influenced by the valency of RNA and by the rates of RNA run-off from polysomes. The latter is further supported by recent single molecule imaging studies. Furthermore, it was estimated that only about 15% of the total mRNA in the cell is localized to stress granules, suggesting that stress granules only influence a minority of mRNA in the cell and may not be as important for mRNA processing as previously thought. That said, these studies represent only a snapshot in time, and it is likely that a larger fraction of mRNA are at one point stored in stress granules due to those RNA transiting in and out.
The stress proteins that are the main component of stress granules in plant cells are molecular chaperones that sequester, protect, and possibly repair proteins that unfold during heat and other types of stress. Therefore, any association of mRNA with stress granules may simply be a side effect of the association of partially unfolded RNA-binding proteins with stress granules, similar to the association of mRNA with proteasomes.
RNA damage
DHX9 is a distinct stress granule that has helicase activity capable of acting on double-stranded RNA, but not on DNA, to promote cell survival. DHX9 acts as a non-membrane bound cytoplasmic compartment to safeguard daughter cells from parental RNA damage. Assembly of DHX9 stress granules appears to be a dedicated mechanism in mammalian cells for protecting against RNA crosslinking damage.Formation
Environmental stressors trigger cellular signaling, eventually leading to the formation of stress granules. In vitro, these stressors can include heat, cold, oxidative stress, endoplasmic reticulum stress, proteasome inhibition, hyperosmotic stress, ultraviolet radiation, inhibition of eIF4A, nitric oxide accumulation after treatment with 3-morpholinosydnonimine, perturbation of pre-mRNA splicing, and other stressors, like puromycin, which result in disassembled polysomes. Many of these stressors result in the activation of particular stress-associated kinases, translational inhibition and stress granule formation. Stress granules will also form upon Gαq activation in a mechanism that involves the release of stress granule associated proteins from the cytosolic population of the Gαq effector phospholipase Cβ.Stress granule formation is often downstream of the stress-activated phosphorylation of eukaryotic translation initiation factor eIF2α; this does not hold true for all types of stressors that induce stress granules, for instance, eIF4A inhibition. Further downstream, prion-like aggregation of the protein TIA-1 promotes the formation of stress granules. The term prion-like is used because aggregation of TIA-1 is concentration dependent, inhibited by chaperones, and because the aggregates are resistant to proteases. It has also been proposed that microtubules play a role in the formation of stress granules, perhaps by transporting granule components. This hypothesis is based on the fact that disruption of microtubules with the chemical nocodazole blocks the appearance of the granules. Furthermore, many signaling molecules have been shown to regulate the formation or dynamics of stress granules; these include the "master energy sensor" AMP-activated protein kinase, the O-GlcNAc transferase enzyme, and the pro-apoptotic kinase ROCK1.
Potential roles of RNA-RNA interactions
RNA phase transitions driven in part by intermolecular RNA-RNA interactions may play a role in stress granule formation. Similar to intrinsically disordered proteins, total RNA extracts are capable of undergoing phase separation in physiological conditions in vitro. RNA-seq analyses demonstrate that these assemblies share a largely overlapping transcriptome with stress granules, with RNA enrichment in both being predominately based on the length of the RNA. Further, stress granules contain many RNA helicases, including the DEAD/H-box helicases /DDX3, eIF4A1, and RHAU. In yeast, catalytic ded1 mutant alleles give rise to constitutive stress granules ATPase-deficient DDX3X mutant alleles are found in pediatric medulloblastoma, and these coincide with constitutive granular assemblies in patient cells. These mutant DDX3 proteins promote stress granule assembly in HeLa cells. In mammalian cells, RHAU mutants lead to reduced stress granule dynamics. Thus, some hypothesize that RNA aggregation facilitated by intermolecular RNA-RNA interactions plays a role in stress granule formation, and that this role may be regulated by RNA helicases. There is also evidence that RNA within stress granules is more compacted, compared to RNA in the cytoplasm, and that the RNA is found to be post-translationally modified by N6-methyladenosine on its 5' ends or RNA acetylation ac4C. Recent work has shown that the highly abundant translation initiation factor and DEAD-box protein eIF4A limits stress granule formation. It does so through its ability to bind ATP and RNA, acting analogously to protein chaperones like Hsp70.Connection with processing bodies
Stress granules and P-bodies share RNA and protein components, both appear under stress, and can physically associate with one another. As of 2018, of the ~660 proteins identified as localizing to stress granules, ~11% also have been identified as processing body-localized proteins. The protein G3BP1 is necessary for the proper docking of processing bodies and stress granules to each other, which may be important for the preservation of polyadenylated mRNA.Although some protein components are shared between stress granules and processing bodies, the majority of proteins in either structure are uniquely localized to either structure. While both stress granules and P-bodies are associated with mRNA, processing bodies have been long proposed to be sites of mRNA degradation because they contain enzymes such as DCP1/2 and XRN1 that are known to degrade mRNA. However, others have demonstrated that mRNA associated with processing bodies are largely translationally repressed but not degraded. It has also been proposed that mRNA selected for degradation are passed from stress granules to processing bodies, though there is also data suggesting that processing bodies precede and promote stress granule formation.
Protein composition of stress granules
The complete proteome of stress granules is still unknown, but efforts have been made to catalog all of the proteins that have been experimentally demonstrated to transit into stress granules. Importantly, different stressors can result in stress granules with different protein components. Many stress granule-associated proteins have been identified by transiently stressing cultured cells and utilizing microscopy to detect the localization of a protein of interest either by expressing that protein fused to a fluorescent protein and/or by fixing cells and using antibodies to detect the protein of interest along with known protein markers of stress granules.In 2016, stress granule "cores" were experimentally identified and then biochemically purified for the first time. Proteins in the cores were identified in an unbiased manner using mass spectrometry. This technical advance lead to the identification of hundreds of new stress granule-localized proteins.
The proteome of stress granules has also been experimentally determined by using two slightly different proximity labeling approaches. One of these proximity labeling approaches is the ascorbate peroxidase method, in which cells are engineered to express a known stress granule protein, such as G3BP1, fused to a modified ascorbate peroxidase enzyme called APEX. Upon incubating the cells in biotin and treating the cells with hydrogen peroxide, the APEX enzyme will be briefly activated to biotinylate all proteins in close proximity to the protein of interest, in this case G3BP1 within stress granules. Proteins that are biotinylated can then be isolated via streptavidin and identified using mass spectrometry. The APEX technique was used to identify ~260 stress granule-associated proteins in several cell types, including neurons, and with various stressors. Of the 260 proteins identified in this study, ~143 had not previously been demonstrated to be stress granule-associated.
Another proximity labeling method used to determine the proteome of stress granules is BioID. BioID is similar to the APEX approach, in that a biotinylating protein was expressed in cells as a fusion protein with several known stress granule-associated proteins. Proteins in close proximity to BirA* will be biotinylated and are then identified by mass spectrometry. Youn et al. used this method to identify/predict 138 proteins as stress granule-associated and 42 as processing body-associated.
A curated database of stress granule-associated proteins can be found here .
The following is a list of proteins that have been demonstrated to localize to stress granules :
| Gene ID | Protein Name | Description | References | Also found in processing bodies? |
| ABCF1 | ABCF1 | ATP Binding Cassette Subfamily F Member 1 | ||
| ABRACL | ABRACL | ABRA C-Terminal Like | ||
| ACAP1 | ACAP1 | ArfGAP With Coiled-Coil, Ankyrin Repeat And PH Domains 1 | ||
| ACBD5 | ACBD5 | Acyl-CoA Binding Domain Containing 5 | ||
| ACTBL2 | ACTBL2 | Beta-actin-like protein 2 | yes | |
| ACTR1A | ACTR1A | Alpha-centractin | ||
| ACTR1B | ACTR1B | Beta-centractin | ||
| ADAR | ADAR1 | Adenosine Deaminase, RNA Specific | ||
| ADD1 | Adducin 1 | Adducin 1 | ||
| AGO1 | Argonaute 1/EIF2C1 | Argonaute 1, RISC Catalytic Component | yes | |
| AGO2 | Argonaute 2 | Argonaute 2, RISC Catalytic Component | yes | |
| AKAP8 | AKAP8 | A-Kinase Anchoring Protein 8 | ||
| AKAP9 | AKAP350 | A-Kinase Anchoring Protein 9 | ||
| AKAP13 | AKAP13/LBC | A-Kinase Anchoring Protein 13 | ||
| ALDH18A1 | ALDH18A1 | Delta-1-pyrroline-5-carboxylate synthase | ||
| ALG13 | ALG13 | ALG13, UDP-N-Acetylglucosaminyltransferase Subunit | ||
| ALPK2 | ALPK2/HAK | Alpha Kinase 2 | ||
| AMOTL2 | AMOTL2/LCCP | Angiomotin Like 2 | ||
| ANKHD1 | ANKHD1 | Ankyrin Repeat and KH Domain Containing 1 | yes | |
| ANKRD17 | ANKRD17/MASK2/GTAR | Ankyrin Repeat Domain 17 | yes | |
| ANG | Angiogenin | Angiogenin | ||
| ANP32E | ANP32E | Acidic leucine-rich nuclear phosphoprotein 32 family member E | ||
| ANXA1 | ANXA1 | Annexin A1 | ||
| ANXA11 | ANXA11 | Annexin 11 | ||
| ANXA6 | ANXA6 | Annexin 6 | ||
| ANXA7 | ANXA7 | Annexin 7 | ||
| APEX1 | APEX1 | DNA- lyase | ||
| APOBEC3C | APOBEC3C | Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3C | ||
| APOBEC3G | APOBEC3G | Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3G | ||
| ARID2 | ARID2/BAF200 | AT-Rich Interaction Domain 2 | ||
| ARPC1B | ARPC1B | Actin-related protein 2/3 complex subunit 1B | ||
| AHSA1 | AHA1 | Activator Of HSP90 ATPase Activity 1 | ||
| AQR | AQR/IBP160 | Aquarius Intron-Binding Spliceosomal Factor | ||
| ARMC6 | ARMC6 | Armadillo Repeat Containing 6 | ||
| ASCC1 | ASCC1 | Activating Signal Cointegrator 1 Complex Subunit 1 | ||
| ASCC3 | ASCC3 | Activating Signal Cointegrator 1 Complex Subunit 3 | ||
| ATAD2 | ATAD2 | ATPase family AAA domain-containing protein 2 | ||
| ATAD3A | ATAD3A | ATPase family AAA domain-containing protein 3A | yes | |
| ATG3 | ATG3 | Autophagy Related 3 | ||
| ATP5A1 | ATP5A1 | ATP synthase subunit alpha, mitochondrial | ||
| ATP6V1G1 | ATP6V1G1/ATP6G | ATPase H+ Transporting V1 Subunit G1 | ||
| ATXN2 | Ataxin 2 | Ataxin 2 | ||
| ATXN2L | Ataxin-2 like | Ataxin 2 Like | ||
| BAG3 | BAG3 | BAG family molecular chaperone regulator 3 | ||
| BANF1 | BANF1 | Barrier-to-autointegration factor | ||
| BAZ1B | BAZ1B | Bromodomain Adjacent To Zinc Finger Domain 1B | ||
| BAZ2A | BAZ2A | Bromodomain Adjacent To Zinc Finger Domain 2A | ||
| BCCIP | BCCIP | BRCA2 And CDKN1A Interacting Protein | ||
| BCLAF1 | BCLAF1 | BCL2 Associated Transcription Factor 1 | ||
| BICC1 | BICC1 | BicC Family RNA Binding Protein 1 | ||
| BIRC2 | BIRC2/CIAP1 | Baculoviral IAP Repeat Containing 2 | ||
| BLM | BLM | BLM RecQ Like Helicase | ||
| BOD1L1 | BOD1L1/FAM44A | Biorientation Of Chromosomes In Cell Division 1 Like 1 | ||
| BOLL | BOULE | Boule Homolog, RNA Binding Protein | ||
| BRAT1 | BRAT1 | BRCA1-associated ATM activator 1 | ||
| BRF1 | BRF1 | BRF1, butyrate response factor-1 | ||
| BTG3 | BTG3 | BTG Anti-Proliferation Factor 3 | yes | |
| C9orf72 | C9orf72 | Uncharacterized protein C9orf72 | ||
| C15orf52 | C15orf52 | Uncharacterized protein C15orf52 | ||
| C20orf27 | C20orf72 | Chromosome 20 Open Reading Frame 27 | ||
| C2CD3 | C2CD3 | C2 Calcium Dependent Domain Containing 3 | ||
| CALML5 | CALML5 | Calmodulin-like protein 5 | ||
| CALR | Calreticulin/CRT | Calreticulin | ||
| CAMSAP1 | CAMSAP1 | Calmodulin Regulated Spectrin Associated Protein 1 | ||
| CAP1 | CAP1 | Adenylyl cyclase-associated protein 1 | ||
| CAPRIN1 | Caprin-1 | Cell Cycle Associated Protein 1 | ||
| CAPZA2 | CAPZA2 | F-actin-capping protein subunit alpha-2 | ||
| CAPZB | CAPZB | Capping Actin Protein Of Muscle Z-Line Subunit Beta | ||
| CARHSP1 | CARHSP1 | Calcium-regulated heat stable protein 1 | ||
| CASC3 | MLN51/BTZ | Cancer Susceptibility 3 | ||
| CBFB | CBFB | Core-binding factor subunit beta | ||
| CBS | CBS | Cystathionine Beta-Synthase | ||
| CBX1 | CBX1 | Chromobox protein homolog 1 | ||
| CBX3 | CBX3 | Chromobox protein homolog 3 | ||
| CCAR1 | CARP-1 | Cell Division Cycle and Apoptosis Regulator 1 | ||
| CCDC9 | CCDC9 | Coiled-Coil Domain Containing 9 | ||
| CCDC9B | CCDC9B | Coiled-Coil Domain Containing 9B | ||
| CCDC124 | CCDC124 | Coiled-Coil Domain Containing 124 | ||
| CCDC85C | CCDC85C | Coiled-Coil Domain Containing 85C | ||
| CCT3 | CCT3 | T-complex protein 1 subunit gamma | ||
| CCT6A | CCT6A | T-complex protein 1 subunit zeta | ||
| CDC20 | CDC20 | Cell Division Cycle 20 | ||
| CDC37 | CDC37 | Cell Division Cycle 37 | ||
| CDC5L | CDC5L | Cell division cycle 5-like protein | ||
| CDC73 | CDC73 | Parafibromin | ||
| CDK1 | CDK1 | Cyclin-dependent kinase 1 | ||
| CDK2 | CDK2 | Cyclin Dependent Kinase 2 | ||
| CDV3 | CDV3 | CDV3 Homolog | ||
| CELF1 | CUGBP1 | CUGBP Elav-Like Family Member 1 | ||
| CELF2 | CUGBP2/BRUNOL3 | CUGBP Elav-Like Family Member 2 | ||
| CELF3 | CUGBP3/BRUNOL1 | CUGBP Elav-Like Family Member 3 | ||
| CENPB | CENPB | Major centromere autoantigen B | ||
| CENPF | CENPF | Centromere Protein F | ||
| CEP78 | CEP78/CRDHL | Centrosomal Protein 78 | ||
| CEP85 | CEP85/CCDC21 | Centrosomal Protein 78 | ||
| CERKL | Ceramide-Kinase Like | Ceramide Kinase Like | ||
| CFL1 | Cofilin-1 | Cofilin-1 | ||
| CHCHD3 | CHCHD3 | Coiled-coil-helix-coiled-coil-helix domain-containing protein 3, mitochondrial | ||
| CHORDC1 | CHORDC1/CHP1 | Cysteine and histidine-rich domain-containing protein 1 | ||
| CIRBP | CIRP | Cold Inducible RNA Binding Protein | ||
| CIT | CIT | Citron Rho-interacting kinase | ||
| CLIC4 | CLIC4 | Chloride intracellular channel protein 4 | ||
| CLNS1A | CLNS1A | Chloride Nucleotide-Sensitive Channel 1A | ||
| CLPP | CLPP | Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit | ||
| CNBP | ZNF9 | CCHC-Type Zinc Finger Nucleic Acid Binding Protein | ||
| CNN3 | CNN3 | Calponin-3 | ||
| CNOT1 | CNOT1/CCR4 | CCR4-Not Transcription Complex Subunit 1 | yes | |
| CNOT10 | CNOT10 | CCR4-Not Transcription Complex Subunit 10 | yes | |
| CNOT11 | CNOT11 | CCR4-Not Transcription Complex Subunit 11 | yes | |
| CNOT2 | CNOT2 | CCR4-Not Transcription Complex Subunit 2 | yes | |
| CNOT3 | CNOT3 | CCR4-Not Transcription Complex Subunit 3 | yes | |
| CNOT4 | CNOT4 | CCR4-Not Transcription Complex Subunit 4 | yes | |
| CNOT6 | CNOT6 | CCR4-Not Transcription Complex Subunit 6 | yes | |
| CNOT6L | CNOT6L | CCR4-Not Transcription Complex Subunit 6L | yes | |
| CNOT7 | CNOT7 | CCR4-Not Transcription Complex Subunit 7 | yes | |
| CNOT8 | CNOT8 | CCR4-Not Transcription Complex Subunit 8 | yes | |
| CNOT9 | CNOT9 | CCR4-Not Transcription Complex Subunit 9 | ||
| CORO1B | CORO1B | Coronin-1B | ||
| CPB2 | Carboxypeptidase B2 | Carboxypeptidase B2 | ||
| CPEB1 | CPEB | Cytoplasmic Polyadenylation Element Binding Protein 1 | ||
| CPEB4 | CPEB4 | Cytoplasmic Polyadenylation Element Binding Protein 4 | yes | |
| CPSF3 | CPSF3 | Cleavage and polyadenylation specificity factor subunit 3 | ||
| CPSF6 | CPSF6 | Cleavage and polyadenylation specificity factor subunit 6 | ||
| CPSF7 | CPSF7 | Cleavage and polyadenylation specificity factor subunit 7 | ||
| CPVL | CPVL | Carboxypeptidase, Vitellogenic Like | yes | |
| CRKL | CRKL | CRK Like Proto-Oncogene, Adaptor Protein | ||
| CROCC | CROCC | Ciliary Rootlet Coiled-Coil, Rootletin | ||
| CRYAB | CRYAB | Alpha-crystallin B chain | ||
| CRYBG1 | CRYBG1 | Crystallin Beta-Gamma Domain Containing 1 | ||
| CSDE1 | CSDE1 | Cold shock domain-containing protein E1 | ||
| CSE1L | CSE1L/XPO2/Exportin-2 | Exportin-2 | ||
| CSNK2A1 | Casein Kinase 2 alpha | Casein Kinase 2 Alpha 1 | ||
| CSTB | Cystatin B | Cystatin B | ||
| CSTF1 | CSTF1 | Cleavage stimulation factor subunit 1 | ||
| CTNNA2 | CTNNA2 | Catenin alpha-2 | ||
| CTNND1 | CTNND1 | Catenin delta-1 | ||
| CTTNBP2NL | CTTNBP2NL | CTTNBP2 N-terminal-like protein | ||
| CWC22 | CWC22 | Pre-mRNA-splicing factor CWC22 homolog | ||
| DAZAP1 | DAZAP1 | DAZ-associated protein 1 | ||
| DAZAP2 | PRTB | DAZ Associated Protein 2 | ||
| DAZL | DAZL1 | Deleted In Azoospermia Like | ||
| DCD | DCD | Dermcidin | ||
| DCP1A | DCP1a | Decapping mRNA 1a | yes | |
| DCP1B | DCP1b | Decapping mRNA 1b | yes | |
| DCP2 | DCP2 | Decapping mRNA 2 | ||
| DCTN1 | DCTN1 | Dynactin subunit 1 | ||
| DDX1 | DEAD box protein 1 | DEAD-Box Helicase 1 | ||
| DDX11 | DEAD box protein 11 | DEAD-Box Helicase 11 | ||
| DDX19A | DDX19A | ATP-dependent RNA helicase DDX19A | ||
| DDX21 | DDX21 | Nucleolar RNA helicase 2 | yes | |
| DDX3 | DEAD box protein 3 | DEAD-Box Helicase 3 | ||
| DDX3X | DDX3X | DEAD-Box Helicase 3, X-Linked | ||
| DDX3Y | DDX3Y | DEAD-Box Helicase 3, Y-Linked | ||
| DDX31 | DDX31 | DEAD-Box Helicase 31 | ||
| DDX47 | DDX47 | Probable ATP-dependent RNA helicase DDX47 | ||
| DDX50 | DDX50 | ATP-dependent RNA helicase DDX50 | yes | |
| DDX58 | RIG-I | DExD/H-Box Helicase 58 | ||
| DDX6 | DEAD box protein 6 | DEAD-Box Helicase 6 | yes | |
| DERA | DERA | Deoxyribose-Phosphate Aldolase | ||
| DGCR8 | DGCR8 | DGCR8 Microprocessor Complex Subunit | ||
| DHX30 | DHX30 | Putative ATP-dependent RNA helicase DHX30 | yes | |
| DHX33 | DHX33 | DEAH-Box Helicase 33 | ||
| DHX36 | RHAU | DEAH-Box Helicase 36 | ||
| DHX57 | DHX57 | DExH-Box Helicase 57 | ||
| DHX58 | LGP2 | DExH-Box Helicase 58 | ||
| DIDO1 | DIDO1 | Death Inducer-Obliterator 1 | ||
| DIS3L2 | DIS3L2/FAM3A | DIS3 Like 3'-5' Exoribonuclease 2 | ||
| DISC1 | Disrupted in Schizophrenia 1 | Disrupted In Schizophrenia 1 | ||
| DKC1 | DKC1 | dyskerin; H/ACA ribonucleoprotein complex subunit 4 | ||
| DNAI1 | Axonemal Dynein Intermediate Chain 1 | Dynein Axonemal Intermediate Chain 1 | ||
| DNAJA1 | DNAJA1 | DnaJ homolog subfamily A member 1 | ||
| DNAJC8 | DNAJC8 | DnaJ homolog subfamily C member 8 | ||
| DOCK4 | DOCK4 | Dedicator Of Cytokinesis 4 | ||
| DPYSL2 | DPYSL2 | Dihydropyrimidinase-related protein 2 | ||
| DPYSL3 | DPYSL3 | Dihydropyrimidinase-related protein 3 | ||
| DROSHA | DROSHA | Drosha Ribonuclease III | ||
| DSP | DSP | Desmoplakin | ||
| DST | DST | Dystonin | ||
| DSTN | DSTN | Destrin | ||
| DTL | DTL | Denticleless E3 Ubiquitin Protein Ligase Homolog | ||
| DTX3L | DTX3L | E3 ubiquitin-protein ligase DTX3L | ||
| DUSP12 | DUSP12/YVH1 | Dual Specificity Phosphatase 12 | ||
| DYNC1H1 | Cytoplasmic Dynein Heavy Chain 1 | Dynein Cytoplasmic 1 Heavy Chain 1 | ||
| DYNLL1 | Cytoplasmic Dynein Light Polypeptide | Dynein Light Chain LC8-Type 1 | ||
| DYNLL2 | DYNLL2 | Dynein light chain 2, cytoplasmic | ||
| DYRK3 | DYRK3 | Dual Specificity Tyrosine Phosphorylation Regulated Kinase 3 | ||
| DZIP1 | DZIP1 | DAZ Interacting Zinc Finger Protein 1 | ||
| DZIP3 | DZIP3 | DAZ Interacting Zinc Finger Protein 3 | ||
| EDC3 | EDC3 | Enhancer of mRNA Decapping 3 | yes | |
| EDC4 | EDC4 | Enhancer of mRNA-Decapping protein 4 | yes | |
| EIF1 | EIF1 | Eukaryotic Translation Initiation Factor 1 | ||
| EIF2A | EIF2A | Eukaryotic Translation Initiation Factor 2A | ||
| EIF2AK2 | Protein Kinase R/PKR | Eukaryotic Translation Initiation Factor 2 Alpha Kinase 2 | ||
| EIF2B1-5 | EIF2B | Eukaryotic Translation Initiation Factor 2B | ||
| EIF2S1 | EIF2A subunit 1 | Eukaryotic Translation Initiation Factor 2 Subunit Alpha | ||
| EIF2S2 | EIF2A subunit 2 | Eukaryotic Translation Initiation Factor 2 Subunit Beta | ||
| EIF3A | EIF3A | Eukaryotic Translation Initiation Factor 3 Subunit A | ||
| EIF3B | EIF3B | Eukaryotic Translation Initiation Factor 3 Subunit B | ||
| EIF3C | EIF3C | Eukaryotic Translation Initiation Factor 3 Subunit C | ||
| EIF3D | EIF3D | Eukaryotic translation initiation factor 3 subunit D | ||
| EIF3E | EIF3E | Eukaryotic translation initiation factor 3 subunit E | ||
| EIF3F | EIF3F | Eukaryotic translation initiation factor 3 subunit F | ||
| EIF3G | EIF3G | Eukaryotic translation initiation factor 3 subunit G | ||
| EIF3H | EIF3H | Eukaryotic translation initiation factor 3 subunit H | ||
| EIF3I | EIF3I | Eukaryotic translation initiation factor 3 subunit I | ||
| EIF3J | EIF3J | Eukaryotic translation initiation factor 3 subunit J | ||
| EIF3K | EIF3K | Eukaryotic translation initiation factor 3 subunit K | ||
| EIF3L | EIF3L | Eukaryotic translation initiation factor 3 subunit L | ||
| EIF3M | EIF3M | Eukaryotic translation initiation factor 3 subunit M | ||
| EIF4A1 | EIF4A1 | Eukaryotic Translation Initiation Factor 4A1 | ||
| EIF4A2 | EIF4A2 | Eukaryotic Translation Initiation Factor 4A2 | ||
| EIF4A3 | EIF4A3 | Eukaryotic Translation Initiation Factor 4A3 | ||
| EIF4B | EIF4B | Eukaryotic translation Initiation factor 4B | ||
| EIF4E | EIF4E | Eukaryotic Translation Initiation Factor 4E | yes | |
| EIF4E2 | EIF4E2 | Eukaryotic Translation Initiation Factor 4E Family Member 2 | yes | |
| EIF4E3 | EIF4E3 | Eukaryotic Translation Initiation Factor 4E Family Member 3 | ||
| EIF4ENIF1 | EIF4ENIF1 | Eukaryotic Translation Initiation Factor 4E Nuclear Import Factor 1 | yes | |
| EIF4G1 | EIF4G1 | Eukaryotic Translation Initiation Factor 4G1 | ||
| EIF4G2 | EIF4G2 | Eukaryotic Translation Initiation Factor 4G2 | ||
| EIF4G3 | EIF4G3 | Eukaryotic Translation Initiation Factor 4G3 | ||
| EIF4H | EIF4H | Eukaryotic translation Initiation factor 4H | ||
| EIF5A | EIF5A | Eukaryotic Translation Initiation Factor 5A | ||
| ELAVL1 | HuR | ELAV Like RNA Binding Protein 1 | yes | |
| ELAVL2 | ELAVL2 | ELAV-like protein 2 | yes | |
| ELAVL3 | ELAVL3/HuC | ELAV Like RNA Binding Protein 3 | ||
| ELAVL4 | HuD | ELAV Like RNA Binding Protein 4 | ||
| ENC1 | ENC1 | Ectodermal-Neural Cortex 1 | ||
| ENDOV | EndoV | Endonuclease V | ||
| ENTPD1 | ENTPD1 | Ectonucleoside Triphosphate Diphosphohydrolase 1 | ||
| EP400 | EP400 | E1A Binding Protein P400 | ||
| EPPK1 | EPPK1 | Epiplakin | ||
| ETF1 | ETF1 | Eukaryotic peptide chain release factor subunit 1 | ||
| EWSR1 | EWSR1 | EWS RNA Binding Protein 1 | ||
| FABP5 | FABP5 | Fatty Acid Binding Protein 5 | ||
| FAM120A | FAM120A/OSSA | Constitutive coactivator of PPAR-gamma-like protein 1 | yes | |
| FAM120C | FAM120C | Family With Sequence Similarity 120C | ||
| FAM168A | FAM168A | Family With Sequence Similarity 168 Member A | ||
| FAM168B | FAM168B/MANI | Family With Sequence Similarity 168 Member B | ||
| FAM83H | FAM83H | Family With Sequence Similarity 83 Member H | ||
| FAM98A | FAM98A | Family With Sequence Similarity 98 Member A | ||
| FAM98C | FAM98C | Family With Sequence Similarity 98 Member C | ||
| FASTK | FAST | Fas Activated Serine/Threonine Kinase | yes | |
| FBL | FBL | rRNA 2-O-methyltransferase fibrillarin | ||
| FBRSL1 | Fibrosin Like 1 | Fibrosin Like 1 | ||
| FHL1 | FHL1 | Four and a half LIM domains protein 1 | ||
| FKBP1A | FKBP1A | FKBP Prolyl Isomerase 1A | ||
| FLNB | FLNB | Filamin-B | ||
| FMR1 | FMRP | Fragile X Mental Retardation 1 | ||
| FNDC3B | FNDC3B | Fibronectin type III domain-containing protein 3B | ||
| FSCN1 | FSCN1 | Fascin | ||
| FTSJ3 | FTSJ3 | pre-rRNA processing protein FTSJ3 | ||
| FUBP1 | FUBP1 | Far Upstream Element Binding Protein 1 | ||
| FUBP3 | FUBP3 | Far upstream element-binding protein 3 | ||
| FUS | FUS | FUS RNA Binding Protein | ||
| FXR1 | FXR1 | FMR1 Autosomal Homolog 1 | ||
| FXR2 | FXR2 | FMR1 Autosomal Homolog 2 | ||
| G3BP1 | G3BP1 | G3BP Stress Granule Assembly Factor 1 | ||
| G3BP2 | G3BP2 | G3BP Stress Granule Assembly Factor 2 | ||
| GABARAPL2 | GABARAPL2/GEF2/ATG8 | GABA Type A Receptor Associated Protein Like 2 | ||
| GAK | GAK | Cyclin G Associated Kinase | ||
| GAR1 | GAR1 | H/ACA Ribonucleoprotein Complex Subunit 1 | ||
| GCA | Grancalcin | Grancalcin | ||
| GEMIN5 | Gemin-5 | Gem Nuclear Organelle Associated Protein 5 | ||
| GFPT1 | GFPT1 | Glutamine—fructose-6-phosphate aminotransferase 1 | ||
| GIGYF1 | GIGYF1/PERQ1 | GRB10 Interacting GYF Protein 1 | ||
| GIGYF2 | GIGYF2/TNRC15/PARK11/PERQ2 | GRB10 Interacting GYF Protein 2 | yes | |
| GLE1 | GLE1 | GLE1, RNA Export Mediator | ||
| GLO1 | Glyoxalase | Glyoxalase | ||
| GLRX3 | GLRX3/Glutaredoxin 3/TNLX2 | Glutaredoxin 3 | ||
| GLUD1 | GLUD1 | Glutamate Dehydrogenase 1 | ||
| GNB2 | GNB2 | Guanine nucleotide-binding protein G/G/G subunit beta-2 | ||
| GOLGA2 | Golgin A2 | Golgin A2 | ||
| GPAT3 | GPAT3 | Glycerol-3-Phosphate Acyltransferase 3 | ||
| GRB2 | GRB2/ASH | Growth Factor Receptor Bound Protein 2 | ||
| GRB7 | GRB7 | Growth Factor Receptor Bound Protein 7 | ||
| GRSF1 | GRSF1 | G-Rich RNA Sequence Binding Factor 1 | ||
| GSPT1 | eRF3 | G1 To S Phase Transition 1 | ||
| GTF2I | GTF2I | General Transcription Factor IIi | ||
| GTF3C1 | GTF3C1 | General Transcription Factor IIIC Subunit 1 | ||
| GTF3C4 | GTF3C4 | General Transcription Factor IIIC Subunit 4 | ||
| H1F0 | H1F0 | Histone H1.0 | ||
| H1FX | H1FX | Histone H1x | ||
| H2AFV | H2AFV | Histone H2A.V | ||
| HABP4 | Ki-1/57 | Hyaluronan Binding Protein 4 | ||
| HDAC6 | HDAC6 | Histone Deacetylase 6 | ||
| HDLBP | HDL-Binding Protein/VGL/Vigilin | High Density Lipoprotein Binding Protein | ||
| HELZ | HELZ | Probable helicase with zinc finger domain | yes | |
| HELZ2 | HELZ2 | Helicase with zinc finger domain 2 | ||
| HMGA1 | HMGA1 | High mobility group protein HMG-I/HMG-Y | ||
| HMGB3 | HMGB3 | High mobility group protein B3 | ||
| HMGN1 | HMGN1 | Non-histone chromosomal protein HMG-14 | ||
| HNRNPA1 | HnRNPA1 | Heterogeneous Nuclear Ribonucleoprotein A1 | ||
| HNRNPA2B1 | HnRNPA2/B1 | Heterogeneous Nuclear Ribonucleoprotein A2/B1 | ||
| HNRNPA3 | HNRNPA3 | Heterogeneous nuclear ribonucleoprotein A3 | ||
| HNRNPAB | HNRNPAB | Heterogeneous nuclear ribonucleoprotein A/B | ||
| HNRNPD | HNRNPD | Heterogeneous nuclear ribonucleoprotein D | ||
| HNRNPDL | HNRNPDL | Heterogeneous nuclear ribonucleoprotein D-like | ||
| HNRNPF | HNRNPF | Heterogeneous nuclear ribonucleoprotein F | ||
| HNRNPH1 | HNRNPH1 | Heterogeneous nuclear ribonucleoprotein H1 | ||
| HNRNPH2 | HNRNPH2 | Heterogeneous nuclear ribonucleoprotein H2 | ||
| HNRNPH3 | HNRNPH3 | Heterogeneous nuclear ribonucleoprotein H3 | ||
| HNRNPK | HNRNPK | Heterogeneous Nuclear Ribonucleoprotein K | ||
| HNRNPUL1 | HNRNPUL1 | Heterogeneous nuclear ribonucleoprotein U-like protein 2 | ||
| HSBP1 | HSBP1 | Heat Shock Factor Binding Protein 1 | ||
| HSP90AA1 | HSP90 | Heat shock protein HSP 90-alpha | ||
| HSPA4 | HSP70 RY | Heat shock 70 kDa protein 4 | ||
| HSPA9 | HSP70 9B | Stress-70 protein, mitochondrial | ||
| HSPB1 | HSP27 | Heat Shock Protein Family B Member 1 | yes | |
| HSPB8 | HSPB8 | Heat Shock Protein Family B Member 8 | ||
| HSPBP1 | HSPBP1 | HSPA Binding Protein 1 | ||
| HSPD1 | HSPD1 | 60 kDa heat shock protein, mitochondrial | ||
| HTT | Huntingtin | Huntingtin | ||
| IBTK | IBTK | Inhibitor Of Bruton Tyrosine Kinase | ||
| IFIH1 | MDA5 | Interferon Induced With Helicase C Domain 1 | ||
| IGF2BP1 | IGF2BP1 | Insulin-like Growth Factor 2 mRNA-binding protein 1 | yes | |
| IGF2BP2 | IGF2BP2 | Insulin-like Growth Factor 2 mRNA-binding protein 2 | yes | |
| IGF2BP3 | IGF2BP3 | Insulin-like Growth Factor 2 mRNA Binding Protein 3 | yes | |
| IK | IK | Protein Red | ||
| ILF3 | NF90 | Interleukin Enhancer Binding Factor 3 | yes | |
| IPO7 | IPO7 | Importin-7 | ||
| IPPK | IP5K | Inositol-Pentakisphosphate 2-Kinase | ||
| ITGB1 | ITGB1 | Integrin beta-1 | ||
| JMJD6 | JMJD6 | Arginine Demethylase and Lysine Hydroxylase | ||
| KANK2 | KANK2 | KN motif and ankyrin repeat domain-containing protein 2 | ||
| KEAP1 | KEAP1/KLHL19 | Kelch Like ECH Associated Protein 1 | ||
| KHDRBS1 | Sam68 | KH RNA Binding Domain Containing, Signal Transduction Associated 1 | ||
| KHDRBS3 | KHDRBS3 | KH domain-containing, RNA-binding, signal transduction-associated protein 3 | ||
| KHSRP | KSRP/FBP2 | KH-Type Splicing Regulatory Protein | ||
| KIAA0232 | KIAA0232 | KIAA0232 | yes | |
| KIAA1524 | CIP2A | Protein CIP2A | ||
| KIF1B | KIF1B | Kinesin Family Member 1B | ||
| KIF13B | KIF13B/GAKIN | Kinesin Family Member 13B | ||
| KIF23 | KIF23 | Kinesin-like protein KIF23 | yes | |
| KIF2A | Kinesin Heavy Chain Member 2 | Kinesin Family Member 2A | ||
| KLC1 | Kinesin Light Chain 1 | Kinesin Light Chain 1 | ||
| KPNA1 | Importin-ɑ5 | Karyopherin Subunit Alpha 1 | ||
| KPNA2 | Importin-ɑ1 | Karyopherin Subunit Alpha 2 | ||
| KPNA3 | Importin-ɑ4 | Karyopherin Subunit Alpha 3 | ||
| KPNA6 | Importin-ɑ7 | Importin subunit alpha | ||
| KPNB1 | Importin-β1 | Karyopherin Subunit Beta 1 | ||
| L1RE1 | LINE1 ORF1p | LINE1 ORF1 protein | ||
| LANCL1 | LanC Like 1 | LanC Like 1 | ||
| LARP1 | LARP1 | La-related protein 1 | ||
| LARP1B | LARP1B | La-related protein 1b | ||
| LARP4 | La-Related protein 4 | La Ribonucleoprotein Domain Family Member 4 | ||
| LARP4B | LARP4B | La Ribonucleoprotein Domain Family Member 4B | ||
| LASP1 | LIM And SH3 Protein 1/MLN50 | LIM And SH3 Protein 1 | ||
| LBR | LBR | Lamin-B receptor | ||
| LEMD3 | LEMD3 | Inner nuclear membrane protein Man1 | ||
| LIG3 | DNA Ligase 3 | DNA Ligase 3 | ||
| LIN28A | LIN28A | Lin-28 Homolog A | ||
| LIN28B | LIN28B | Lin-28 Homolog B | ||
| LMNA | LMNA | Prelamin-A/C | ||
| LPP | LPP | Lipoma-preferred partner | ||
| LSM1 | LSM1 | LSM1 Homolog, mRNA Degradation Associated | yes | |
| LSM12 | LSM12 | LSM12 Homolog | ||
| LSM14A | RAP55 | LSM14A, mRNA Processing Body Assembly Factor | yes | |
| LSM14B | LSM14B | Protein LSM14 homolog B | yes | |
| LSM3 | LSM3 | U6 snRNA-associated Sm-like protein LSm3 | yes | |
| LUC7L | LUC7L | Putative RNA-binding protein Luc7-like 1 | ||
| LUZP1 | LUZP1 | Leucine zipper protein 1 | ||
| MACF1 | MACF1 | Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5 | ||
| MAEL | MAEL | Maelstrom Spermatogenic Transposon Silencer | ||
| MAGEA4 | MAGEA4 | Melanoma-associated antigen 4 | ||
| MAGED1 | MAGED1 | Melanoma-associated antigen D1 | ||
| MAGED2 | MAGED2 | Melanoma-associated antigen D2 | ||
| MAGOHB | MAGOHB | Protein mago nashi homolog 2 | ||
| MAP1LC3A | LC3-I | Microtubule Associated Protein 1 Light Chain 3 Alpha | ||
| MAP4 | MAP4 | Microtubule-associated protein 4 | ||
| MAPK1IP1L | MAPK1IP1L | Mitogen-Activated Protein Kinase 1 Interacting Protein 1 Like | ||
| MAP4K4 | MAP4K4 | Mitogen-activated protein kinase kinase kinase kinase 4 | ||
| MAPK8 | JNK1 | Mitogen-Activated Protein Kinase 8 | ||
| MAPRE1 | MAPRE |