Dynamic Shuttling of Tia-1 Accompanies the Recruitment of mRNA to Mammalian Stress Granules

By N. Kedersha, M. Cho, Wei Li, P. Yacono, Samantha Chen, Natalie Gilks, D. Golan, Paul Anderson. Journal of Cell Biology, 2000

821 citations recorded by the source corpus.

Mammalian stress granules (SGs) harbor untranslated mRNAs that accumulate in cells exposed to environmental stress. Drugs that stabilize polysomes (emetine) inhibit the assembly of SGs, whereas drugs that destabilize polysomes (puromycin) promote the assembly of SGs. Moreover, emetine dissolves preformed SGs as it promotes the assembly of polysomes, suggesting that these mRNP species (i.e., SGs and polysomes) exist in equilibrium. We used green flourescent protein–tagged SG-associated RNA-binding proteins (specifically, TIA-1 and poly[A] binding protein [PABP-I]) to monitor SG assembly, disassembly, and turnover in live cells. Fluorescence recovery after photobleaching shows that both TIA-1 and PABP-I rapidly and continuously shuttle in and out of SGs, indicating that the assembly of SGs is a highly dynamic process. This unexpected result leads us to propose that mammalian SGs are sites at which untranslated mRNAs are sorted and processed for either reinitiation, degradation, or packaging into stable nonpolysomal mRNP complexes. A truncation mutant of TIA-1 (TIA-1ΔRRM), which acts as a transdominant inhibitor of SG assembly, promotes the expression of cotransfected reporter genes in COS transfectants, suggesting that this process of mRNA triage might, directly or indirectly, influence protein expression.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/507c774cf635e3b7acfe489d9295de29db7c5226

How researchers see this paper

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In Molecular Biology

1. R. Parker
2. Paul Anderson
3. N. Kedersha
4. S. Alberti
5. P. Ivanov
6. C. J. Decker
7. Saumya Jain
8. Joshua R. Wheeler

Citations in the corpus

• Evidence that ternary complex (eIF2-GTP-tRNA(i)(Met))-deficient preinitiation complexes are core constituents of mammalian stress granules. (2002, background): “…5 end of a polysomal mRNA will allow elongating ribosomes to “run off” the transcript, effectively converting the mRNA from a polysome into a 48S* mRNP. Emetine treatment prevents this, allowing small amounts of TIA-1 to be shifted into the polysome region of the gradient (Kedersha et al., 2000).”
• Tar DNA Binding Protein-43 (TDP-43) Associates with Stress Granules: Analysis of Cultured Cells and Pathological Brain Tissue (2010, background): “Conversely, puromycin (20 mg/ml, 3 hrs), which stimulates SG formation [17], increased formation of TDP-4386–414 and full-length TDP-43 inclusions (Fig.”
• Protein Phase Separation: A New Phase in Cell Biology (2018, background): “Inhibiting polysome disassembly prevents SG formation, even when the stress response is activated [18].”
• Stress granules and processing bodies are dynamically linked sites of mRNP remodeling (2005, background): “During stress, mRNA continues to be directed to sites of reinitiation, but in the absence of eIF2–GTP–tRNA Met , it shuttles back to SGs, where it accumulates (Kedersha et al., 2000). mRNAs within SGs are not degraded, making them available for rapid reinitiation in cells that recover from stress.”
• P-bodies and stress granules: possible roles in the control of translation and mRNA degradation. (2012, background): “…mRNAs in polysomes by blocking translation elongation decreases P-bodies and stress granules even during continued stress, which suggests that mRNAs in these compartments are in dynamic equilibrium with polysomes (Kedersha et al. 2000; Cougot et al. 2004; Teixeira et al. 2005; Mollet et al. 2008).”
• G3BP–Caprin1–USP10 complexes mediate stress granule condensation and associate with 40S subunits (2016, background): “In all cases, agents that stabilize polysomes prevent or reverse SG assembly, highlighting the dynamic relationship between SGs and polysomes (Kedersha et al., 2000).”
• Stress granules: the Tao of RNA triage. (2008, background): “TIA-1, TIAR, G3BP, PABP-1 and TTP) shuttle through SGs much more rapidly than changes in SG morphology would suggest [14, 25 ].”
• The stress granule transcriptome reveals principles of mRNA accumulation in stress granules (2017, positive): “This is consistent with prior models that mRNAs engaged with ribosomes are restricted from entering SGs and provides additional evidence that mRNAs need to be nontranslating to accumulate within SG (Kedersha et al., 2000) (Kedersha and Anderson, 2002).”
• RNA granules: post-transcriptional and epigenetic modulators of gene expression (2009, background): “These agents dissolve PBs and SGs by depleting their core constituent”
• Processing bodies require RNA for assembly and contain nontranslating mRNAs. (2005, background): “Stress granules contain translation initiation factors, small ribosomal subunits, and the mRNA-binding proteins TIA and TIA-R (Kedersha et al. 2002), whereas P-bodies contain mRNA decay factors (Ingelfinger et al. 2002; Lykke-Andersen 2002; van Dijk et al. 2002; Cougot et al. 2004).”
• AU-rich elements and associated factors: are there unifying principles? (2006, background): “It is now known that stress granules and P-bodies are affected by drugs that inhibit translation; cycloheximide and emetine that ‘freeze’ polysomes cause disassembly of stress granules and P-bodies whereas puromycin that dismantles polysomes promotes the assembly of stress granules (112,130).”
• Phase separation in biology; functional organization of a higher order (2016, background): “Removal of the stress signals and re-initiation of mRNA translation caused stress granules to disassemble [36].”