Recycling of Eukaryotic Posttermination Ribosomal Complexes

Pisarev, Andrey V.; Hellen, Christopher U.T.; Pestova, Tatyana V.

doi:10.1016/j.cell.2007.08.041

Cited by 199 publications

(252 citation statements)

References 31 publications

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“…23 and 46 and references therein). In vitro transcribed tRNA i Met was aminoacylated using recombinant E. coli methionyl tRNA synthetase, whereas total native tRNAs were aminoacylated with Met, Val, His, and Leu using native aminoacyl-tRNA synthetases (46).…”

Section: Methodsmentioning

confidence: 99%

Cryo-EM structure of the mammalian eukaryotic release factor eRF1–eRF3-associated termination complex

Taylor

Unbehaun

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Eukaryotic translation termination results from the complex functional interplay between two eukaryotic release factors, eRF1 and eRF3, and the ribosome, in which GTP hydrolysis by eRF3 couples codon recognition with peptidyl-tRNA hydrolysis by eRF1. Here, using cryo-electron microscopy (cryo-EM) and flexible fitting, we determined the structure of eRF1-eRF3-guanosine 5′- [β,γ-imido] triphosphate (GMPPNP)-bound ribosomal pretermination complex (pre-TC), which corresponds to the initial, pre-GTP hydrolysis stage of factor attachment. Our results show that eukaryotic translation termination involves a network of interactions between the two release factors and the ribosome. Our structure provides mechanistic insight into the coordination between GTP hydrolysis by eRF3 and subsequent peptide release by eRF1.T ermination of translation occurs when a ribosome reaches the end of the coding region and a stop codon (UAA, UAG, or UGA) enters the aminoacyl tRNA binding site (A site), leaving peptidyl-tRNA in the peptidyl tRNA binding site (P site). It entails stop codon recognition by specialized release factors followed by hydrolysis of peptidyl-tRNA. In eukaryotes, termination is mediated by the concerted action of two directly interacting release factors, eRF1 and eRF3. eRF1 is responsible for stop codon recognition and inducing hydrolysis of peptidyl-tRNA, whereas eRF3, a ribosome-dependent GTPase, strongly stimulates peptide release by eRF1 in a GTP-dependent manner (for review, see ref. 1).eRF1 also participates in ribosome recycling: after peptide release it remains associated with the ribosome and together with ATP-binding cassette sub-family E member 1 (ABCE1) promotes splitting the ribosome into free 60S and tRNA/mRNA-associated 40S subunits (2). eRF1 and eRF3 have paralogs, Dom34 (yeast)/ Pelota (mammals) and Hbs1, respectively, which do not participate in termination but instead play a key role in No-go and nonstop decay surveillance mechanisms (e.g., see refs. 3, 4). Dom34/Pelota and Hbs1 do not induce peptide release in a mechanism similar to eRFs. Instead, they cooperate with ABCE1 to promote dissociation of stalled elongation complexes, which is accompanied by peptidyltRNA drop off (5-7). eRF1 comprises N-terminal (N), middle (M), and C-terminal (C) domains (8). The N domain is responsible for stop codon recognition, which is achieved through a 3D network of conserved residues that include apical TASNIKS (amino acid sequence: threonine-alanine-serine-asparagine-isoleucine-lysine-serine) and YxCxxxF motifs (e.g., refs. 9-12). Domain M contains the universally conserved GGQ motif, which is critical for triggering peptide release: as shown for prokaryotes, its placement into the peptidyl transferase center (PTC) causes rRNA rearrangement, allowing a water molecule to enter (for review, see ref. 13). The rigid core of domain C forms an α-β sandwich (8) that deviates from the standard form by the presence of a small insertion, which forms a minidomain (14). eRF3 consists of an N-terminal sequence (residues 1-...

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Section: Methodsmentioning

confidence: 99%

Cryo-EM structure of the mammalian eukaryotic release factor eRF1–eRF3-associated termination complex

Taylor

Unbehaun

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…15 Unfortunately, models showing that the antiassociation activity of eIF3 is relevant in vivo have not been produced. Intriguingly, eIF3e and eIF3h subunits as well as eIF6 and ribosomal protein rpL24 (see below) are .…”

Section: Eif6-mediated Control Of 60s Availability and 80s Formation mentioning

confidence: 99%

Translational control by 80S formation and 60S availability: The central role of eIF6, a rate limiting factor in cell cycle progression and tumorigenesis

Brina¹,

Grosso²,

Miluzio³

et al. 2011

Cell Cycle

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“…[12][13][14][15] After translation termination and ribosome recycling, the 40S and 60S subunits get dissociated, stripped of the mRNA, P-site deacylated tRNA and polypeptide release factor eRF1. 18,19 The process of ribosome recycling aided by ATP-binding cassette (ABC) protein ABCE1, eIF3, eIF1 and eIF1A leads to "regeneration" of 40S subunits that become competent for initiation. 18,19 Binding of the 40S subunit to multisubunit factor eIF3 prevents association of 40S and 60S subunits, thus enabling formation and engagement of 40S eIF3 eIF1/ 1A TC complex in the next round of initiation.…”

Section: Introductionmentioning

confidence: 99%

“…18,19 The process of ribosome recycling aided by ATP-binding cassette (ABC) protein ABCE1, eIF3, eIF1 and eIF1A leads to "regeneration" of 40S subunits that become competent for initiation. 18,19 Binding of the 40S subunit to multisubunit factor eIF3 prevents association of 40S and 60S subunits, thus enabling formation and engagement of 40S eIF3 eIF1/ 1A TC complex in the next round of initiation. However, in contrast to the situation in prokaryotes, for most eukaryotic mRNAs, the PIC, 43S complex, comprised of 40S, eIF3, eIF1/ 1A and TC does not land directly on the AUG start codon, binding instead to the 5' end of the mRNA.…”

Section: Introductionmentioning

confidence: 99%

Eukaryote-specific extensions in ribosomal proteins of the small subunit: Structure and function

Ghosh

Komar

2015

Translation

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Keywords: conserved ribosomal proteins, eukaryotic/yeast ribosome, eukaryote-specific extensions, eukaryotic translation initiation factors, protein synthesis, small ribosomal subunitHigh-resolution structures of yeast ribosomes have improved our understanding of the architecture and organization of eukaryotic rRNA and proteins, as well as eukaryote-specific extensions present in some conserved ribosomal proteins. Despite this progress, assignment of specific functions to individual proteins and/or eukaryotespecific protein extensions remains challenging. It has been suggested that eukaryote-specific extensions of conserved proteins from the small ribosomal subunit may facilitate eukaryote-specific reactions in the initiation phase of protein synthesis. This review summarizes emerging data describing the structural and functional significance of eukaryotespecific extensions of conserved small ribosomal subunit proteins, particularly their possible roles in recruitment and spatial organization of eukaryote-specific initiation factors.

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Recycling of Eukaryotic Posttermination Ribosomal Complexes

Cited by 199 publications

References 31 publications

Cryo-EM structure of the mammalian eukaryotic release factor eRF1–eRF3-associated termination complex

Cryo-EM structure of the mammalian eukaryotic release factor eRF1–eRF3-associated termination complex

Translational control by 80S formation and 60S availability: The central role of eIF6, a rate limiting factor in cell cycle progression and tumorigenesis

Eukaryote-specific extensions in ribosomal proteins of the small subunit: Structure and function

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