1. Ribosomal mistranslation leads to silencing of the unfolded protein response and increased mitochondrial biogenesis
- Author
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Heithem Boukari, Youjin Teo, Ivan Osinnii, James M. Moore, Eric Westhof, Stefan Duscha, Dmitri Shcherbakov, Adrian Cortes-Sanchon, Hubert Rehrauer, Margarita Brilkova, Reda Juskeviciene, Endre Laczko, Rashid Akbergenov, Matilde Mantovani, Harshitha Santhosh Kumar, Erik C. Böttger, Functional Genomics Center Zurich, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, and Böttger, Erik C
- Subjects
Ribosomal Proteins ,[SDV]Life Sciences [q-bio] ,Medicine (miscellaneous) ,610 Medicine & health ,1100 General Agricultural and Biological Sciences ,Biology ,Endoplasmic Reticulum ,Ribosome ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,1300 General Biochemistry, Genetics and Molecular Biology ,Gene expression ,Gene silencing ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Protein folding ,RNA, Messenger ,Transcriptomics ,lcsh:QH301-705.5 ,030304 developmental biology ,0303 health sciences ,Messenger RNA ,Organelle Biogenesis ,Protein transport ,10179 Institute of Medical Microbiology ,Endoplasmic reticulum ,Gene Expression Profiling ,2701 Medicine (miscellaneous) ,Translation (biology) ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,G1 Phase Cell Cycle Checkpoints ,Cell biology ,Mitochondria ,HEK293 Cells ,Mitochondrial biogenesis ,lcsh:Biology (General) ,Amino Acid Substitution ,Protein Biosynthesis ,Mutation ,Unfolded protein response ,Proteostasis ,Unfolded Protein Response ,570 Life sciences ,biology ,General Agricultural and Biological Sciences ,Ribosomes ,030217 neurology & neurosurgery - Abstract
Translation fidelity is the limiting factor in the accuracy of gene expression. With an estimated frequency of 10−4, errors in mRNA decoding occur in a mostly stochastic manner. Little is known about the response of higher eukaryotes to chronic loss of ribosomal accuracy as per an increase in the random error rate of mRNA decoding. Here, we present a global and comprehensive picture of the cellular changes in response to translational accuracy in mammalian ribosomes impaired by genetic manipulation. In addition to affecting established protein quality control pathways, such as elevated transcript levels for cytosolic chaperones, activation of the ubiquitin-proteasome system, and translational slowdown, ribosomal mistranslation led to unexpected responses. In particular, we observed increased mitochondrial biogenesis associated with import of misfolded proteins into the mitochondria and silencing of the unfolded protein response in the endoplasmic reticulum., Communications Biology, 2, ISSN:2399-3642
- Published
- 2019
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