Translation Initiation Regulated by RNA-Binding Protein in Mammals: The Modulation of Translation Initiation Complex by Trans-Acting Factors

Fukao, Akira; Tomohiro, Takumi; Fujiwara, Toshinobu

doi:10.3390/cells10071711

Cited by 18 publications

(13 citation statements)

References 118 publications

(156 reference statements)

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“…It is known that trans-acting factors, such as RNA-binding proteins (RBPs) and microRNAs (miRNAs), regulate translation through direct or indirect interaction with a basic cap-binding complex to modulate the translation initiation complex (reviewed in [ 41 ]).…”

Section: Resultsmentioning

confidence: 99%

Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A

Abukar

Wipplinger

Hariharan

et al. 2021

Cells

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Mesothelioma is an aggressive cancer associated with asbestos exposure. RNA-binding motif protein 8a (RBM8A) mRNA editing increases in mouse tissues upon asbestos exposure. The aim of this study was to further characterize the role of RBM8A in mesothelioma and the consequences of its mRNA editing. RBM8A protein expression was higher in mesothelioma compared to mesothelial cells. Silencing RBM8A changed splicing patterns in mesothelial and mesothelioma cells but drastically reduced viability only in mesothelioma cells. In the tissues of asbestos-exposed mice, editing of Rbm8a mRNA was associated with increased protein immunoreactivity, with no change in mRNA levels. Increased adenosine deaminase acting on dsRNA (ADAR)-dependent editing of Alu elements in the RBM8A 3′UTR was observed in mesothelioma cells compared to mesothelial cells. Editing stabilized protein expression. The unedited RBM8A 3′UTR had a stronger interaction with Musashi (MSI) compared to the edited form. The silencing of MSI2 in mesothelioma or overexpression of Adar2 in mesothelial cells resulted in increased RBM8A protein levels. Therefore, ADAR-dependent editing contributes to maintaining elevated RBM8A protein levels in mesothelioma by counteracting MSI2-driven downregulation. A wider implication of this mechanism for the translational control of protein expression is suggested by the editing of similarly structured Alu elements in several other transcripts.

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Section: Resultsmentioning

confidence: 99%

Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A

Abukar

Wipplinger

Hariharan

et al. 2021

Cells

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“…Some CTAs have several paralogs and isoforms. The functioning of the core apparatus is accompanied by other proteins, in addition to these factors [1,[10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus

Kachaev

Ivashchenko

Kozlov

et al. 2021

Cells

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Components of the translation apparatus, including ribosomal proteins, have been found in cell nuclei in various organisms. Components of the translation apparatus are involved in various nuclear processes, particularly those associated with genome integrity control and the nuclear stages of gene expression, such as transcription, mRNA processing, and mRNA export. Components of the translation apparatus control intranuclear trafficking; the nuclear import and export of RNA and proteins; and regulate the activity, stability, and functional recruitment of nuclear proteins. The nuclear translocation of these components is often involved in the cell response to stimulation and stress, in addition to playing critical roles in oncogenesis and viral infection. Many components of the translation apparatus are moonlighting proteins, involved in integral cell stress response and coupling of gene expression subprocesses. Thus, this phenomenon represents a significant interest for both basic and applied molecular biology. Here, we provide an overview of the current data regarding the molecular functions of translation factors and ribosomal proteins in the cell nucleus.

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“…Motivated by published meiotic phenotypes associated with mTORi during oocyte maturation and defective asymmetric polar body extrusion [53-55, 62, 63], we assayed potential functional mTOR roles during the first spatial cellular separation in preimplantation mouse embryos. We assayed levels of phospho-4EIF4EBP1 (p4EIF4EBP1), a known product of active mTORC1 signalling [64], at the 8- to 16-cell transition and noted increased p4EIF4EBP1 levels associated with 8-cell stage M-phase entry, that were localised around condensing chromosomes and associated with mitotic spindles; returning to basal levels in 16-cell stage progeny (Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

Spatial positioning of preimplantation mouse embryo blastomeres is regulated by mTORC1 and 7mG-cap dependent translation at the 8- to 16-cell transition

Gahurová

Tomankova

Cerna

et al. 2023

Preprint

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Preimplantation stages of mouse embryo development involve temporal and spatial specification and segregation of three late blastocyst cell lineages; trophectoderm (TE), primitive endoderm (PrE) and epiblast (EPI). Spatial separation of the outer TE lineage from the two inner cell mass (ICM) lineages (PrE and EPI) starts with the 8- to 16-cell transition and concludes following transit through the 16- to 32-cell stages. This results in an early blastocyst ICM derived from descendants of primary founding inner cells and a secondarily contributed population, of which subsequent relative EPI versus PrE potencies are subject to debate. Here, we report generation of primary but not the secondary ICM populations is highly dependent on temporally discreet activation of the mammalian target of Rapamycin (mTOR, specifically mTORC1) during M-phase entry at the 8-cell stage. This role is mediated via regulation of the 7-methylguanosine- (7mG) cap binding initiation complex (EIF4F), linked to translation of a subset of key mRNAs containing 5[prime] UTR terminal oligopyrimidine (TOP-) or TOP-like sequence motifs; as knockdown of identified TOP-like motif containing transcripts also impairs generation of 16-cell stage primary ICM founders. However, mTOR inhibition induced ICM cell number deficits at the early blastocyst stage can be compensated by the late blastocyst stage, in the absence of inhibition. This compensation is likely initiated at the 32-cell stage when supernumerary outer cells in mTOR-inhibited embryos exhibit molecular characteristics of inner cells. Collectively, the data identify a novel mechanism specifically governing initial spatial segregation of blastomeres in the mouse embryo, that is distinct from those directing subsequent inner cell formation and contributes to germane segregation of late blastocyst lineages.

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Translation Initiation Regulated by RNA-Binding Protein in Mammals: The Modulation of Translation Initiation Complex by Trans-Acting Factors

Cited by 18 publications

References 118 publications

Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A

Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A

Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus

Spatial positioning of preimplantation mouse embryo blastomeres is regulated by mTORC1 and 7mG-cap dependent translation at the 8- to 16-cell transition

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