Stress granules are dispensable for mRNA stabilization during cellular stress
Nadine Bley,Marcell Lederer,Birgit Pfalz,Claudia Reinke,Tommy Fuchs,Markus Glaß,Birgit Möller,Stefan Hüttelmaier +7 more
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TLDR
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, which is dispensable for preventing mRNA degradation.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.read more
Citations
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Recognition of RNA N 6 -methyladenosine by IGF2BP proteins enhances mRNA stability and translation
Huilin Huang,Huilin Huang,Hengyou Weng,Hengyou Weng,Wen-Ju Sun,Xi Qin,Xi Qin,Hailing Shi,Hailing Shi,Huizhe Wu,Huizhe Wu,Huizhe Wu,Boxuan Simen Zhao,Boxuan Simen Zhao,Ana Mesquita,Chang Liu,Chang Liu,Celvie L. Yuan,Yueh-Chiang Hu,Stefan Hüttelmaier,Jennifer R. Skibbe,Rui Su,Rui Su,Xiaolan Deng,Xiaolan Deng,Xiaolan Deng,Lei Dong,Lei Dong,Miao Sun,Chenying Li,Chenying Li,Chenying Li,Sigrid Nachtergaele,Sigrid Nachtergaele,Yungui Wang,Yungui Wang,Chao Hu,Chao Hu,Kyle Ferchen,Kenneth D. Greis,Xi Jiang,Xi Jiang,Minjie Wei,Liang-Hu Qu,Jun-Lin Guan,Chuan He,Chuan He,Jian-Hua Yang,Jianjun Chen,Jianjun Chen +49 more
TL;DR: This work reports the insulin-like growth factor 2 mRNA-binding proteins as a distinct family of m6A readers that target thousands of mRNA transcripts through recognizing the consensus GG(m6A)C sequence, and identifies IGF2BPs as an additional class of N6-methyladenosine (m 6A) reader proteins.
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The Stress Granule Transcriptome Reveals Principles of mRNA Accumulation in Stress Granules
Anthony Khong,Anthony Khong,Tyler Matheny,Saumya Jain,Sarah F. Mitchell,Joshua Wheeler,Roy Parker,Roy Parker +7 more
TL;DR: The results suggest that stress granules may not represent a specific biological program of messenger ribonucleoprotein (mRNP) assembly, but instead form by condensation of nontranslating mRNPs in proportion to their length and lack of association with ribosomes.
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RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation
Jordina Guillén-Boixet,Andrii Kopach,Alex S. Holehouse,Sina Wittmann,Marcus Jahnel,Marcus Jahnel,Raimund Schlüßler,Kyoohyun Kim,Irmela R.E.A. Trussina,Jie Wang,Daniel Mateju,Ina Poser,Shovamayee Maharana,Martine Ruer-Gruß,Doris Richter,Xiaojie Zhang,Young-Tae Chang,Jochen Guck,Alf Honigmann,Julia Mahamid,Anthony A. Hyman,Rohit V. Pappu,Simon Alberti,Simon Alberti,Titus M. Franzmann +24 more
TL;DR: It is proposed that condensation coupled to conformational rearrangements and heterotypic multivalent interactions may be a general principle underlying RNP granule assembly.
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Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization
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TL;DR: Inspired by patchy colloid theory, this work proposes a general framework by which competing networks give rise to compositionally specific and tunable condensates, while relative linkage between nodes underlies multiphase organization.
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Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules
Sonja Kroschwald,Shovamayee Maharana,Daniel Mateju,Liliana Malinovska,Elisabeth Nüske,Ina Poser,Doris Richter,Simon Alberti +7 more
TL;DR: It is proposed that the material state of RNP granules is flexible and that the solid state of yeast stressgranules is an adaptation to extreme environments, made possible by the presence of a powerful disaggregation machine.
References
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RNA-Binding Proteins Tia-1 and Tiar Link the Phosphorylation of Eif-2α to the Assembly of Mammalian Stress Granules
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