eIF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondrial Homeostasis, and Muscle Health

Lin, Yingying; Li, Fajin; Huang, Linlu; Polte, Christine; Duan, Haoran; Fang, Jau–Shiung; Sun, Li; Xing, Xudong; Tian, GY; Cheng, Yong; Ignatova, Zoya; Yang, Xuerui; Wolf, Dieter A

doi:10.1016/j.molcel.2020.06.003

Cited by 59 publications

(69 citation statements)

References 74 publications

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“…Importantly, we found that, compared with unselected 40S, eIF2::40S and each of the eIF3::40S are less enriched in the start codon region relative to the 5′ UTR ( Figures 3 G–3I, S5 B–S5D, S6 B, and S6C), supporting the assumption that both eIFs dissociate from PICs during late stages of AUG recognition. The fact that this enrichment is significantly more pronounced for eIF2::40Ss than eIF3::40Ss ( Figures 3 L, S5 E, S6 E, and S6F) indicates that some PICs at start codons still contain eIF3 but not eIF2, which is consistent with the model that eIF2 leaves the PIC upon AUG recognition ( Hinnebusch, 2017 , Shirokikh and Preiss, 2018 , Valášek et al., 2017 ), whereas eIF3 lingers during the initial elongation cycles ( Mohammad et al., 2017 ; see also the related papers in this issue of Molecular Cell , Bohlen et al., 2020 and Lin et al., 2020 ). In support, we observed markedly increased coverage of yeast and human eIF3::80 FPs over unselected 80S FPs within the first ∼20–25 codons past the AUG ( Figures 3 M and S6 J).…”

Section: Resultssupporting

confidence: 81%

Selective Translation Complex Profiling Reveals Staged Initiation and Co-translational Assembly of Initiation Factor Complexes

et al. 2020

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Summary Translational control targeting the initiation phase is central to the regulation of gene expression. Understanding all of its aspects requires substantial technological advancements. Here we modified yeast translation complex profile sequencing (TCP-seq), related to ribosome profiling, and adapted it for mammalian cells. Human TCP-seq, capable of capturing footprints of 40S subunits (40Ss) in addition to 80S ribosomes (80Ss), revealed that mammalian and yeast 40Ss distribute similarly across 5′TRs, indicating considerable evolutionary conservation. We further developed yeast and human selective TCP-seq (Sel-TCP-seq), enabling selection of 40Ss and 80Ss associated with immuno-targeted factors. Sel-TCP-seq demonstrated that eIF2 and eIF3 travel along 5′ UTRs with scanning 40Ss to successively dissociate upon AUG recognition; notably, a proportion of eIF3 lingers on during the initial elongation cycles. Highlighting Sel-TCP-seq versatility, we also identified four initiating 48S conformational intermediates, provided novel insights into ATF4 and GCN4 mRNA translational control, and demonstrated co-translational assembly of initiation factor complexes.

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Section: Resultssupporting

confidence: 81%

Selective Translation Complex Profiling Reveals Staged Initiation and Co-translational Assembly of Initiation Factor Complexes

et al. 2020

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“…Mechanistically, RBPMS predominantly associates with translation initiation complexes, and its loss leads to the aberrant retention of translation initiation factors eIF2A, -3H, and -3E, on ribosomal complexes. All these factors have been reported to be involved in translation specialization (Choudhuri et al, 2013;Lin et al, 2020;Shah et al, 2016;Wek, 2018). Importantly, RBPMS loss severely depletes the translation apparatus of the key 'surveillance' factor eIF5A.…”

Section: Discussionmentioning

confidence: 99%

A specialized mRNA translation circuit instated in pluripotency presets the competence for cardiogenesis in humans

Bartsch

Kalamkar

Ahuja

et al. 2021

Preprint

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In mammals, translation is uniquely regulated at the exit of pluripotency to rapidly reprogram the proteome to enable lineage commitment. Yet, the developmental mediators of translational control and their mode-of-action remain elusive. Using human embryonic stem cells, we identified RBPMS as a vital translation specialization factor that allows selective translation of developmental regulators. RBPMS-driven translational control balances the abundance of cell-fate regulators to enable accurate lineage decisions upon receiving differentiation cues. RBPMS loss, without affecting pluripotency, specifically and severely impedes mesoderm specification and subsequent cardiogenesis. Mechanistically, the direct binding of RBPMS to 3 ′UTR allows selective translation of transcripts encoding developmental regulators including integral components of central morphogen signaling networks specifying mesoderm. RBPMS-loss results in aberrant retention of key translation initiation factors on ribosomal complexes. Our data unveil how emerging lineage choices from pluripotency are controlled by translational specialization via ribosomal platforms acting as a regulatory nexus for developmental cell fate decisions.

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“…The RPL5 transcript and protein were upregulated in the ribosomes of NIL-723, and RP protein mediates selective translation 35 , suggesting that RPL5 may be necessary for the translation of specific glutenins. EIF3 is the most complex translation initiation factor and plays a role in translation elongation and enhances the synthesis of proteins associated with membrane function in protein synthesis 36 . EIF3.…”

Section: Discussionmentioning

confidence: 99%

Proteome and transcriptome analyses of wheat near isogenic lines identifies key proteins and genes of wheat bread quality

Zhao

Zhang

et al. 2021

Sci Rep

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The regulation of wheat protein quality is a highly complex biological process involving multiple metabolic pathways. To reveal new insights into the regulatory pathways of wheat glutenin synthesis, we used the grain-filling period wheat grains of the near-isogenic lines NIL-723 and NIL-1010, which have large differences in quality, to perform a combined transcriptome and proteome analysis. Compared with NIL-1010, NIL-723 had 1287 transcripts and 355 proteins with significantly different abundances. Certain key significantly enriched pathway were identified, and wheat quality was associated with alanine, aspartate and glutamate metabolism, nitrogen metabolism and alpha-linolenic acid metabolism. Differentially expressed proteins (DEPs) or Differentially expressed genes (DEGs) in amino acid synthesis pathways were upregulated primarily in the glycine (Gly), methionine (Met), threonine (Thr), glutamic acid (Glu), proline (proC), cysteine (Cys), and arginine (Arg) synthesis and downregulated in the tryptophan (trpE), leucine (leuC), citrulline (argE), and ornithine (argE) synthesis. Furthermore, to elucidate changes in glutenin in the grain synthesis pathway, we plotted a regulatory pathway map and found that DEGs and DEPs in ribosomes (RPL5) and the ER (HSPA5, HYOU1, PDIA3, PDIA1, Sec24, and Sec31) may play key roles in regulating glutenin synthesis. The transcriptional validation of some of the differentially expressed proteins through real-time quantitative PCR analysis further validated the transcriptome and proteomic results.

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eIF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondrial Homeostasis, and Muscle Health

Cited by 59 publications

References 74 publications

Selective Translation Complex Profiling Reveals Staged Initiation and Co-translational Assembly of Initiation Factor Complexes

Selective Translation Complex Profiling Reveals Staged Initiation and Co-translational Assembly of Initiation Factor Complexes

A specialized mRNA translation circuit instated in pluripotency presets the competence for cardiogenesis in humans

Proteome and transcriptome analyses of wheat near isogenic lines identifies key proteins and genes of wheat bread quality

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