title: Stress granules are dispensable for mRNA stabilization during cellular stress.
abstract: During cellular stress, protein synthesis is severely reduced and bulk mRNA is recruited to stress granules (SGs). Previously, we showed that the SG-recruited IGF2 mRNA-binding protein 1 (IGF2BP1) interferes with target mRNA degradation during cellular stress. Whether this requires the formation of SGs remained elusive. Here, we demonstrate that the sustained inhibition of visible SGs requires the concomitant knockdown of TIA1, TIAR and G3BP1. FRAP and photo-conversion studies, however, indicate that these proteins only transiently associate with SGs. This suggests that instead of forming a rigid scaffold for mRNP recruitment, TIA proteins and G3BP1 promote SG-formation by constantly replenishing mRNPs. In contrast, RNA-binding proteins like IGF2BP1 or HUR, which are dispensable for SG-assembly, are stably associated with SGs and the IGF2BP1/HUR-G3BP1 association is increased during stress. The depletion of IGF2BP1 enhances the degradation of target mRNAs irrespective of inhibiting SG-formation, whereas the turnover of bulk mRNA remains unaffected when SG-formation is impaired. Together these findings indicate that the stabilization of mRNAs during cellular stress is facilitated by the formation of stable mRNPs, which are recruited to SGs by TIA proteins and/or G3BP1. Importantly, however, the aggregation of mRNPs to visible SGs is dispensable for preventing mRNA degradation.
authors.affiliation: Division of Molecular Cell Biology, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany Core Facility Imaging (CFI) of the Medical Faculty, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Bley
authors.affiliation: Division of Molecular Cell Biology, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany.
authors.forename: Marcell
authors.initials: M
authors.lastname: Lederer
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Pfalz
authors.affiliation: Division of Molecular Cell Biology, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany Core Facility Imaging (CFI) of the Medical Faculty, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Reinke
authors.affiliation: Division of Molecular Cell Biology, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany.
authors.forename: Tommy
authors.initials: T
authors.lastname: Fuchs
authors.affiliation: Division of Molecular Cell Biology, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany Core Facility Imaging (CFI) of the Medical Faculty, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Glaß
authors.affiliation: Institute of Computer Science, Martin Luther University Halle-Wittenberg, Von-Seckendorff-Platz 1, 06099 Halle, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Möller
authors.affiliation: Division of Molecular Cell Biology, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany Core Facility Imaging (CFI) of the Medical Faculty, Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 1, 06120 Halle, Germany stefan.huettelmaier@medizin.uni-halle.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hüttelmaier
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004265:DNA Helicases; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C406144:IGF2BP1 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases