ABCE1: A special factor that orchestrates translation at the crossroad between recycling and initiation

Mancera-Martínez, Eder; Querido, Jailson Brito; Valášek, Leoš Shivaya; Simonetti, Angelita; Hashem, Yaser

doi:10.1080/15476286.2016.1269993

Cited by 64 publications

(62 citation statements)

References 56 publications

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“…It is important to note that in Simonetti et al. we made an attempt to assign another intersubunit-side based density that we observed in our near-native conditions directly in cell extracts to the mammalian eIF3g–i unit ( 70 ); however, this density later turned out to be ABCE1 ( 71 , 72 ). Nonetheless, taken into account that the interaction between the eIF3b-extended α-helix and the eIF3g–i unit is highly conserved, it seems very likely that the entire eIF3a-CTD–b–g–i module relocates from the solvent-exposed side to the intersubunit side, so that the eIF3b-RRM interacts with 18S rRNA and eIF1 and the eIF3b-propeller interacts with eIF2γ (Figure 4B ).…”

Section: The Eif3 Structure Assembly and Placement In The 48s Pre-inmentioning

confidence: 75%

Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle

Valášek¹,

Zeman²,

Wagner³

et al. 2017

Nucleic Acids Research

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122

138

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Protein synthesis is mediated via numerous molecules including the ribosome, mRNA, tRNAs, as well as translation initiation, elongation and release factors. Some of these factors play several roles throughout the entire process to ensure proper assembly of the preinitiation complex on the right mRNA, accurate selection of the initiation codon, errorless production of the encoded polypeptide and its proper termination. Perhaps, the most intriguing of these multitasking factors is the eukaryotic initiation factor eIF3. Recent evidence strongly suggests that this factor, which coordinates the progress of most of the initiation steps, does not come off the initiation complex upon subunit joining, but instead it remains bound to 80S ribosomes and gradually falls off during the first few elongation cycles to: (1) promote resumption of scanning on the same mRNA molecule for reinitiation downstream—in case of translation of upstream ORFs short enough to preserve eIF3 bound; or (2) come back during termination on long ORFs to fine tune its fidelity or, if signaled, promote programmed stop codon readthrough. Here, we unite recent structural views of the eIF3–40S complex and discus all known eIF3 roles to provide a broad picture of the eIF3’s impact on translational control in eukaryotic cells.

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Section: The Eif3 Structure Assembly and Placement In The 48s Pre-inmentioning

confidence: 75%

Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle

Valášek¹,

Zeman²,

Wagner³

et al. 2017

Nucleic Acids Research

Self Cite

122

138

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“…6h), thus very likely excluding a direct active role of ABCE1 in the assembly of the initiation complex. It is reasonable to assume that in the cell ABCE1 undergoes on/off cycles to the IC in an ATP-dependent manner, as we have previously suggested 18 . However, these results do not contradict the demonstrated function for ABCE1 as an anti-ribosomal-subunit association factor.…”

Section: Abce1 Binding To the Initiation Complex Is Ntp-dependentmentioning

confidence: 89%

Structural insights into the mammalian late-stage initiation complexes

Simonetti

Guca

Bochler

et al. 2019

Preprint

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SUMMARYIn higher eukaryotes, the mRNA sequence in direct vicinity of the start codon, called the Kozak sequence (CRCCaugG, where R is a purine), is known to influence the rate of the initiation process. However, the molecular basis underlying its role remains poorly understood. Here, we present the cryo-electron microscopy (cryo-EM) structures of mammalian late-stage 48S initiation complexes (LS48S IC) in the presence of two different native mRNA sequences, β-globin and histone 4 (H4) at overall resolution of 3Å and 3.5Å, respectively. Our high-resolution structures unravel key interactions from the mRNA to eukaryotic initiation factors (eIF): 1A, 2, 3, 18S rRNA, and several 40S ribosomal proteins. In addition, we were able to study the structural role of ABCE1 in the formation of native 48S ICs. Our results reveal a comprehensive map of the ribosome/eIFs –mRNA and –tRNA interactions and suggest the impact of mRNA sequence on the structure of the LS48S IC.

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“…even after ribosomal recycling and most likely also promotes the initiation phase in close co-operation with eIF3 45,46 further suggests that eIF4G could, via its direct connection with eIF3, modulate ribosomal recycling in a way that would favor dissociation of only the 60S subunit and deacylated tRNA, which would stimulate REI. Since reinitiation-as a molecular phenomenon-is also rather interesting from the medical point of view (there is a rapidly growing number of articles reporting contributions of defective uORF functions to various human diseases 10 ), more work is certainly needed to fully understand the mechanistic aspects of this intriguing difference, as well as the reinitiation mechanism as a whole.…”

Section: Discussionmentioning

confidence: 99%

Does eIF3 promote reinitiation after translation of short upstream ORFs also in mammalian cells?

et al. 2017

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Reinitiation after translation of short upstream ORFs (uORFs) represents one of the means of regulation of gene expression on the mRNA-specific level in response to changing environmental conditions. Over the years it has been shown-mainly in budding yeast-that its efficiency depends on cis-acting features occurring in sequences flanking reinitiation-permissive uORFs, the nature of their coding sequences, as well as protein factors acting in trans. We earlier demonstrated that the first two uORFs from the reinitiation-regulated yeast GCN4 mRNA leader carry specific structural elements in their 5' sequences that interact with the translation initiation factor eIF3 to prevent full ribosomal recycling post their translation. Actually, this interaction turned out to be instrumental in stabilizing the mRNA·40S post-termination complex, which is thus capable to eventually resume scanning and reinitiate on the next AUG start site downstream. Recently, we also provided important in vivo evidence strongly supporting the long-standing idea that to stimulate reinitiation, eIF3 has to remain bound to ribosomes elongating these uORFs until their stop codon has been reached. Here we examined the importance of eIF3 and sequences flanking uORF1 of the human functional homolog of yeast GCN4, ATF4, in stimulation of efficient reinitiation. We revealed that the molecular basis of the reinitiation mechanism is conserved between yeasts and humans.

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ABCE1: A special factor that orchestrates translation at the crossroad between recycling and initiation

Cited by 64 publications

References 56 publications

Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle

Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle

Structural insights into the mammalian late-stage initiation complexes

Does eIF3 promote reinitiation after translation of short upstream ORFs also in mammalian cells?

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