Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules.
Nancy Kedersha,Michael Cho,Wei Li,Patrick W. Yacono,Samantha Chen,Natalie Gilks,David E. Golan,Paul A. Anderson +7 more
Reads0
Chats0
TLDR
Fluorescence recovery after photobleaching shows that both TIA-1 and PABP-I rapidly and continuously shuttle in and out ofSGs, indicating that the assembly of SGs is a highly dynamic process, and proposes that mammalian SGs are sites at which untranslated mRNAs are sorted and processed for either reinitiation, degradation, or packaging into stable nonpolysomal mRNP complexes.Abstract:
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.read more
Citations
More filters
Journal ArticleDOI
Liquid phase condensation in cell physiology and disease.
TL;DR: The findings together suggest that several membrane-less organelles have been shown to exhibit a concentration threshold for assembly, a hallmark of phase separation, and represent liquid-phase condensates, which form via a biologically regulated (liquid-liquid) phase separation process.
Journal ArticleDOI
Stress granules and processing bodies are dynamically linked sites of mRNP remodeling
Nancy Kedersha,Georg Stoecklin,Maranatha Ayodele,Patrick W. Yacono,Jens Lykke-Andersen,Marvin J. Fritzler,Donalyn Scheuner,Randal J. Kaufman,David E. Golan,Paul A. Anderson +9 more
TL;DR: It is proposed that mRNA released from disassembled polysomes is sorted and remodeled at SGs, from which selected transcripts are delivered to PBs for degradation, an interaction that is promoted by the related mRNA decay factors TTP and BRF1.
Journal ArticleDOI
Protein Phase Separation: A New Phase in Cell Biology.
Steven Boeynaems,Steven Boeynaems,Simon Alberti,Nicolas L. Fawzi,Tanja Mittag,Magdalini Polymenidou,Frederic Rousseau,Frederic Rousseau,Joost Schymkowitz,Joost Schymkowitz,James Shorter,Benjamin Wolozin,Ludo Van Den Bosch,Peter Tompa,Peter Tompa,Monika Fuxreiter +15 more
TL;DR: A combination of techniques from cell biology, biophysics, physical chemistry, structural biology, and bioinformatics are starting to help establish the molecular principles of an emerging field, thus paving the way for exciting discoveries, including novel therapeutic approaches for the treatment of age-related disorders.
Journal ArticleDOI
Eukaryotic Stress Granules: The Ins and Outs of Translation
TL;DR: Together, stress granules and P-bodies reveal a dynamic cycle of distinct biochemical and compartmentalized mRNPs in the cytosol, with implications for the control of mRNA function.
Journal ArticleDOI
Stress granules: the Tao of RNA triage
Paul A. Anderson,Nancy Kedersha +1 more
TL;DR: Although both self-assemble in response to stress-induced perturbations in translation, several recent reports reveal novel proteins and RNAs that are components of these structures but also perform other cellular functions.
References
More filters
Journal ArticleDOI
Mobility measurement by analysis of fluorescence photobleaching recovery kinetics.
TL;DR: The theoretical basis and some practical guidelines for simple, rigorous analysis of FPR experiments are presented and some model experiments on aqueous solutions of rhodamine 6G are described.
Journal ArticleDOI
RNA-Binding Proteins Tia-1 and Tiar Link the Phosphorylation of Eif-2α to the Assembly of Mammalian Stress Granules
TL;DR: The ability of a TIA-1 mutant lacking its RNA-binding domains to function as a transdominant inhibitor of SG formation suggests that this RNA- binding protein acts downstream of the phosphorylation of eIF-2α to promote the sequestration of untranslated mRNAs at SGs.
Journal ArticleDOI
Control of translation initiation in animals
Nicola K. Gray,Marvin Wickens +1 more
TL;DR: The current understanding of the mechanisms of regulation of translation initiation is reviewed, drawing particularly on examples in which the biological consequences of the regulation are clear.
Journal ArticleDOI
TIA-1 is a translational silencer that selectively regulates the expression of TNF-α
Monica Piecyk,Stephen Wax,Andreas Beck,Nancy Kedersha,Mita Gupta,Beatrice Maritim,Samantha Chen,Cyril Gueydan,Véronique Kruys,Michel Streuli,Paul A. Anderson +10 more
TL;DR: Mice lacking TIA‐1 are hypersensitive to the toxic effects of LPS, indicating that this translational control pathway may regulate the organismal response to microbial stress.
Journal ArticleDOI
Cytoplasmic heat shock granules are formed from precursor particles and are associated with a specific set of mRNAs.
TL;DR: Ulastructural analysis supports the ribonucleoprotein nature of HSGs and their composition of approximately 10-nm precursor particles and gives a reasonable explanation for the striking conservation of untranslated mRNAs during heat shock and may apply also to animal cells.