PMC

Schematic of SG formation formed via the self-association of TIA proteins (shown in brown with circles representing RRM domains, and a tail representing the C-terminal PRD) bound to stalled ribonucleoprotein-mRNA complexes. Upon phosphorylation of eIF2 under conditions of stress, the pre-initiation complex is stalled. Accumulation of the stalled mRNA complex results in its incorporation into SG (involving interactions between the TIA protein PRDs) until such time that heat shock proteins are able to reverse the process and translation is resumed.

Cartoon representation of TIA protein RNA-recognition motif (RRM) structures solved using NMR spectroscopy. RRM 1 from TIAR (PDB entry:2CQI) and RRMs 2 and 3 from TIA-1 (PDB entry:2MJN) are shown. Amino acid residues of RRMs 2 and 3 shown to be perturbed upon binding by ssRNA are highlighted in ruby showing that binding mainly occurs across the surface the β-sheet, but also involves residues outside the canonical RRM fold [,,,]. No evidence for specific binding of RNA by RRM1 has been observed.

Schematic of the domain structure of T cell restricted intracellular antigen (TIA) protein isoforms. TIA proteins consist of three RNA recognition motifs (RRMs) that provide RNA/DNA binding specificity and a Q-rich prion-related domain (PRD) domain, involved in stress granule (SG) formation. The two isoforms of both proteins that form as a result of alternative splicing are indicated.