Embryonic Lethality of Mutant Mice Deficient in the p116 Gene

Koyanagi-Katsuta, Rimiko; Akimitsu, Nobuyoshi; Hamamoto, Hiroshi; Arimitsu, Nagisa; Hatano, Toshiyuki; Sekimizu, Kazuhisa

doi:10.1093/oxfordjournals.jbchem.a003172

Cited by 9 publications

(11 citation statements)

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“…Deficient mice in the eIF3b and eIF3m genes also display a lethal phenotype (Koyanagi‐Katsuta et al . ; Zeng et al . ).…”

Section: Discussionmentioning

confidence: 99%

“…To date, no direct ontogenic function for eIF3f subunit has been attributed, suggesting that the mortality in our eIF3f −/− individuals is probably mediated by the defect of eIF3f-related specific pathways. Deficient mice in the eIF3b and eIF3m genes also display a lethal phenotype (Koyanagi-Katsuta et al 2002;Zeng et al 2013). The absence of eIF3b mainly results in embryo lethality before the blastocyst stage, demonstrating that this factor is essential for the very early stages of mouse development (Koyanagi-Katsuta et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Deficient mice in the eIF3b and eIF3m genes also display a lethal phenotype (Koyanagi-Katsuta et al 2002;Zeng et al 2013). The absence of eIF3b mainly results in embryo lethality before the blastocyst stage, demonstrating that this factor is essential for the very early stages of mouse development (Koyanagi-Katsuta et al 2002). eIF3b with eIF3a, and c, constitute the conserved functional core of mammalian eIF3 (Masutani et al 2007).…”

Section: Discussionmentioning

confidence: 99%

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eIF3f depletion impedes mouse embryonic development, reduces adult skeletal muscle mass and amplifies muscle loss during disuse

Docquier

Pavlin

Raibon

et al. 2019

The Journal of Physiology

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Key points In muscular cells, eukaryotic initiation factor subunit f (eIF3f) activates protein synthesis by allowing physical interaction between mechanistic target of rapamycin complex 1 (MTORC1) and ribosomal protein S6 kinase 1 (S6K1), although its physiological role in animals is unknown. A knockout approach suggests that homozygous mice carrying a null mutation of the eIF3f gene fail to develop and consequently die at early embryonic stage, whereas heterozygous mice associated with a partial depletion of eIF3f gene grow normally and are phenotypically indistinguishable from wild‐type mice. Heterozygous mice express reduced eIF3f mRNA and protein levels in skeletal muscles and show diminished muscle mass associated with a decrease in the protein synthesis rate and an inhibition of the MTORC1 pathway. During hindlimb immobilization, heterozygous eIF3f mice display an exacerbated immobilization‐induced muscle atrophy associated with reduced protein synthesis. These results highlight the essential role of eIF3f during embryonic development and its involvement in muscular homeostasis via protein synthesis regulation. Abstract Eukaryotic translation initiation factor 3, subunit F (eIF3f), a component of eIF3 complex, plays an important role in protein synthesis regulation, although its physiological functions are unknown. We generated and analysed mice carrying a null mutation in the eIF3f gene. We showed that homozygous eIF3f knockout fail to develop and that eIF3f−/− embryos die at an early stage of development but after the pre‐implantation stage. However, disrupting one eIF3f allele does not affect growth, viability and fertility of heterozygous mice but, instead, reduces eIF3f mRNA and protein levels in all tissues examined. Although heterozygous mice are phenotypically indistinguishable from wild‐type mice, they present a diminished body weight and a lean mass reduction associated with normal body size. Interestingly, skeletal muscles are mainly affected and display an altered cell size without modification of fibre number. Skeletal muscles of heterozygous mice show a deficiency in polysome content, a decrease in protein synthesis rate and an inhibition of the mechanistic target of rapamycin (MTOR) pathway. We then studied the effects of hindlimb immobilization that mimic muscle disuse on heterozygous mice aiming to further explore the involvement of eIF3f in protein synthesis. We found that eIF3f partial depletion amplifies muscle atrophy compared to wild‐type mice. Mass and cross‐sectional area decreases were associated with reduced MTOR pathway activation and protein synthesis rate. Taken together, our data indicate that eIF3f is essential for mice embryonic development and controls adult skeletal muscle mass via protein synthesis regulation in a MTOR‐dependent manner.

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“…Deficient mice in the eIF3b and eIF3m genes also display a lethal phenotype (Koyanagi‐Katsuta et al . ; Zeng et al . ).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

eIF3f depletion impedes mouse embryonic development, reduces adult skeletal muscle mass and amplifies muscle loss during disuse

Docquier

Pavlin

Raibon

et al. 2019

The Journal of Physiology

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show abstract

“…EIF3 subunits accumulate asynchronously during seed development and heat shock (Gallie et al, 1998), suggesting that eIF3 is a dynamic and heterogeneous complex. Only five eIF3 subunits, a, b, c, g, and i, are considered core subunits because they are highly conserved and essential for protein translation in yeast (Asano et al, 1998;Hershey and Merrick, 2000;Koyanagi-Katsuta et al, 2002). Whereas some of the remaining, noncore, eIF3 subunits may still support basal translation, others may play stabilizing or regulatory roles (Bandyopadhyay et al, 2000Crane et al, 2000;Guo et al, 2000;Matsumoto et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Translational Regulation via 5′ mRNA Leader Sequences Revealed by Mutational Analysis of the Arabidopsis Translation Initiation Factor Subunit eIF3h

et al. 2004

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Eukaryotic translation initiation factor 3 (eIF3) consists of core subunits that are conserved from yeast to man as well as less conserved, noncore, subunits with potential regulatory roles. Whereas core subunits tend to be indispensable for cell growth, the roles of the noncore subunits remain poorly understood. We addressed the hypothesis that eIF3 noncore subunits have accessory functions that help to regulate translation initiation, by focusing on the Arabidopsis thaliana eIF3h subunit. Indeed, eIF3h was not essential for general protein translation. However, results from transient expression assays and polysome fractionation indicated that the translation efficiency of specific 59 mRNA leader sequences was compromised in an eif3h mutant, including the mRNA for the basic domain leucine zipper (bZip) transcription factor ATB2/AtbZip11, translation of which is regulated by sucrose. Among other pleiotropic developmental defects, the eif3h mutant required exogenous sugar to transit from seedling to vegetative development, but it was hypersensitive to elevated levels of exogenous sugars. The ATB2 mRNA was rendered sensitive to the eIF3h level by a series of upstream open reading frames. Moreover, eIF3h could physically interact with subunits of the COP9 signalosome, a protein complex implicated primarily in the regulation of protein ubiquitination, supporting a direct biochemical connection between translation initiation and protein turnover. Together, these data implicate eIF3 in mRNA-associated translation initiation events, such as scanning, start codon recognition, or reinitiation and suggest that poor translation initiation of specific mRNAs contributes to the pleiotropic spectrum of phenotypic defects in the eif3h mutant.

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“…EIF3B is evolutionarily conserved and has been shown to be one of six subunits which comprise the functional core of mammalian eIF3. Eif3b À/À embryos die between fertilization and the blastocyst stage, indicating the importance of Eif3b in early embryonic development [Koyanagi-Katsuta et al, 2002]. However, no structural defects have been described in Eif3b þ/À mice.…”

Section: Discussionmentioning

confidence: 99%

Delineation of a less than 200 kb minimal deleted region for cardiac malformations on chromosome 7p22

Richards

Zaveri

Wolf

et al. 2011

American J of Med Genetics Pt A

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Cardiac malformations are commonly seen in individuals with terminal and interstitial deletions involving chromosome band 7p22. Although these malformations represent a significant cause of morbidity, the dosage-sensitive gene(s) that underlie these defects have yet to be identified. In this report, we describe a 16-month-old male with tetralogy of Fallot, bilateral second branchial arch remnants, and mild dysmorphic features. Array comparative genomic hybridization analysis revealed a less than 400 kb interstitial deletion on chromosome 7p22. The deletion was confirmed by real-time quantitative PCR and FISH analyses and was not detected in samples obtained from the child's parents. Molecular data from this de novo deletion, in combination with data from other isolated 7p deletions in the literature, can be used to define a less than 200 kb minimal deleted region for cardiac malformations on 7p22. This minimal deleted region spans all, or portions, of the coding regions of four known genes-MAD1L1, FTSJ2, NUDT1, and SNX8-and may include upstream regulatory elements of EIF3B. It is likely that one or more of these five genes, alone or in combination, plays an important, yet previously uncharacterized, role in cardiac development.

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Embryonic Lethality of Mutant Mice Deficient in the p116 Gene

Cited by 9 publications

References 0 publications

eIF3f depletion impedes mouse embryonic development, reduces adult skeletal muscle mass and amplifies muscle loss during disuse

eIF3f depletion impedes mouse embryonic development, reduces adult skeletal muscle mass and amplifies muscle loss during disuse

Translational Regulation via 5′ mRNA Leader Sequences Revealed by Mutational Analysis of the Arabidopsis Translation Initiation Factor Subunit eIF3h

Delineation of a less than 200 kb minimal deleted region for cardiac malformations on chromosome 7p22

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