Table I.

SG-associated signaling molecules

Stress granule protein	Enzymatic activity	Role in SG assembly/signalling
RSK2 (p90 ribosomal S6 kinase)	Kinase	Modulates both SG assembly and cell survival during arsenite-induced stress 71. Reduced expression of RSK2 inhibits SG assembly and survival of MCF7 cells exposed to arsenite. The N-terminal kinase domain of RSK2 (amino acids 1-389 containing an LC/ID region at 174-187) directly binds to the prion-related C-terminus of TIA-1, which is required for RSK2 recruitment to SGs.
PKCα (protein kinase Cα)	Kinase	Enhances SG assembly in cells subjected to heat shock or arsenite-induced stress 76, possibly by binding to G3BP2, a key regulator of SG assembly 77.
SMG-1	Kinase	Phosphoinositide 3 kinase-like kinase essential for nonsense mediated decay (NMD) that promotes arsenite- or H2O2- (but not heat-) induced SG assembly 78. The SMG-1 substrate Upf1 is also recruited to arsenite-induced SGs 78. Both SMG-1 and Upf1 possess multiple LC/ID regions.
MK-STYX (mitogen-activated protein kinase phosphoserine/threonin e/tyrosine-binding protein)	Pseudo-phosphatase	Structurally related to a family of dual specificity protein tyrosine phosphatases 79, 80. Interacts with the SG-nucleating protein G3BP 81 and inhibits arsenite-induced SG assembly.
Calcineurin	Phosphatase	In cold-shocked Cryptococcus neoformans, the calcineurin catalytic subunit Cna1 is recruited to RNA granules that contain both P-body (Dcp1) and SG (Pub1) markers 82.
AGO-2 (argonaute-2)	Ribonuclease	Recruitment of AGO-2 to SGs 83, 84 correlates with stress-induced reductions in RNA interference by both siRNAs and miRNAs 85, suggesting that AGO-2/RISC sequestration in SGs inhibits or stalls its cleavage of miRNA-targeted transcripts.
Rck/p54	Helicase	Rck/p54 may bind mRNAs released from polysomes due to blocked translation initiation 86 thereby facilitating the repackaging of remodeled mRNPs into RNA granules. Consistent with this model, TTP cooperates with Rck/p54 to inhibit mRNA translation 87.
RHAU	Helicase	The recruitment of RHAU to SGs requires its N-terminal RNA-binding domain 88; targeted knockdown of RHAU does not inhibit SG assembly 88. Possibly RHAU, like Rck/p54, prepares selected mRNAs for movement to SGs.
DDX3/Ded1	Helicase	Overexpression of DDX3 nucleates SG assembly, whereas its knockdown inhibits SG assembly. Its helicase activity is dispensable for SG nucleation, whereas its eIF4E binding is required 89 suggesting that DDX3 may inhibit translation initiation. The helicase activity of DDX3/Ded1 may facilitate a transition from translational repression to active translation, thus allowing mRNA to escape from RNA granules and resume translation at polysomes 90.
Poly(ADP)ribosyltransf erase	ADP ribose polymerase	Individual overexpression of any of six poly (ADP) ribose polymerases nucleates SGs without increasing the phosphorylation of eIF2α, whereas overexpression of two distinct poly (ADP) ribose glycohydrolases inhibits arsenite-induced SG assembly 91. These findings implicate the poly (ADP) ribose modification of SG proteins in SG assembly; but the mechanism remains unclear.
PRMT3 (protein arginine methytransferase 3)	Methyltransfer ase	Responsible for asymmetric dimethylarginine modifications. The methylated tudor domain of TDRD3 promotes its recruitment to SGs 92.
Dnmt2	Methyltransfer ase	Methylates a conserved cytosine residue in the anti-codon loops of tRNAAsp, tRNAVal, and tRNAGly 93. The viability of Drosophila Dnmt2 mutants exposed to heat, paraquat or H2O2 is significantly reduced relative to wild type control flies, implicating this methylation event in the stress response program. Anigogenin-induced tRNA cleavage is also involved in a stress response program in mammalian cells 94–96, therefore Dnmt2-induced methylation of tRNA may prevent angiogenin-induced tRNA cleavage. Indeed, Dnmt2 inhibits angiogenin-induced cleavage of tRNAAsp and tRNAGly, but not tRNAMet. Possibly sequestration of Dnmt2 at SGs prevents tRNA methylation under stress conditions to regulate this stress-response program.
Roquin	Ubiquitin modifying enzyme	Overexpression of full length Roquin or its isolated Roquin domain nucleates SG assembly 97. Recruitment to SGs has been implicated in the activity of the Roquin 1 and Roquin 2 paralogs that promote the degradation of mRNA encoding the co-stimulatory molecules Icos and OX-40 98, 99 to promote autoimmunity. Roquin also binds a stem loop structure to destabilize selected mRNAs 100.
MCPIP1	Ubiquitin modifying enzyme	Possesses both RNAse and deubiquitinating activities 101. Overexpressed MCPIP1 forms cytoplasmic granules that include components of both SGs and P-bodies, but paradoxically block arsenite-induced SG assembly. Splenocytes lacking MCPIP1 exhibit spontaneous SGs without stress, and form more SGs than control splenocytes in response to arsenite, suggesting that MCPIP1 inhibits SG assembly. Point mutants lacking either RNAse or deubiquitinating activities reveal that MCPIP1-induced granule assembly requires its deubiquitinating activity, whereas MCPIP1- induced inhibition of SG assembly requires its RNAse activity.
USP10	Ubiquitin protease	Interacts with G3BP and PABP 73. Knockdown dampens SG assembly in and correlates with increased production of reactive oxygen species (ROS) and increased apoptosis, both of which are reversed by overexpression of WT or deubiquitinase-inactive USP10.