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Fig. 4. Proposed mechanism for the assembly of stress granules. Assembly of an eIF2/eIF5-deficient preinitiation complex at the 5' end of a polysome results in translational arrest (1). As elongating ribosomes `run-off' the mRNA (2,3), the polysome is converted into a 48S* preinitiation complex (4) that is routed by TIA-1 into stress granules (5,6) or productively initiated by the replacement of TIA with eIF5/eIF2/GTP/tRNAmet (green circle). A requirement for HSP 70 and ATP in removing mRNAs from the SG is indicated. Destabilizing elements (red) such as tristetraprolin (TTP) are proposed to direct selected stress granule mRNAs to sites of degradation, whereas stabilizing elements such as HuR (blue) are proposed to direct selected mRNAs to sites of storage and/or reinitiation. By this triage process, the SG may monitor the structure and integrity of mRNP complexes and determine the fate of specific RNAs.





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