Review
Tying up loose ends: ribosome recycling in eukaryotes and archaea

https://doi.org/10.1016/j.tibs.2012.11.003Get rights and content

Ribosome recycling is the final – or first – step of the cyclic process of mRNA translation. In eukaryotes and archaea, dissociation of the two ribosomal subunits proceeds in a fundamentally different way than in bacteria. It requires the ABC-type ATPase ABCE1 [previously named RNase L inhibitor (Rli)1 or host protein (HP)68], but the reaction and its regulation remain enigmatic. Here, we focus on ribosome recycling in its physiological context, including translation termination and reinitiation. The regulation of this crucial event can only be described by a systems biology approach, involving a network of proteins modulating mRNA translation. The key role of ABCE1, and what is known about the structure and function of this versatile protein, is discussed.

Section snippets

Ribosome splitting must occur in distinct cellular pathways

Translation of mRNA takes place in four steps: initiation, elongation, termination, and ribosome recycling. During recycling, the ribosome is split into the small and large subunits (from 80S into 40S and 60S in eukaryotes; from 70S into 30S and 50S in archaea and bacteria) 1, 2. Ribosome recycling serves as the link between translation termination and initiation because a new round of translation is initiated by various factors on the released small ribosomal subunit [3]. Ribosome recycling

Ribosome recycling: a comparison between the three domains of life

Although protein biosynthesis is generally conserved, there are striking differences between bacteria (Figure 1a), archaea (Figure 1b), and eukaryotes (Figure 1c). In all cases, translation termination and ribosome recycling involve numerous translation factors (Box 1). It is through these translation factors and a series of nucleotide exchange and hydrolysis events on the ribosome that translation termination and ribosome recycling are coupled and regulated [8]. In all domains of life,

mRNA quality control: ribosome recycling in case of emergency

The mRNA surveillance pathway is initiated when the ribosome is stalled and further elongation is prevented [4] (Figure 1d). The eukaryotic mRNA surveillance pathways, no-go decay (NGD) [13] and no-stop decay (NSD) 14, 15, require ABCE1 6, 8. The proteins Dom34 (yeast)/Pelota (mammals) and their interaction partner Hbs1 (GTPase) are paralogs of the eRF1–eRF3 system [16]. Similarly, these proteins are recruited to the A site of stalled ribosomes as a ternary complex (step 1). GTP hydrolysis by

Multitasking of cellular functions by ABCE1

The strong sequence conservation of ABCE1 in eukaryotes and archaea (67% identity between human and yeast, 49% identity between human and the closest archaeal ortholog from Methanocaldococcus fervens) indicates a fundamental and essential function for this enzyme 20, 21. Initially, ABCE1 was discovered as RNase L inhibitor (Rli1) (Figure 2) [12]. RNase L plays a significant role in the inhibition of cellular protein synthesis and the resistance to viral infection. Double-stranded (viral) RNA

Structure and conformational dynamics of ABCE1

Several structures of ABCE1 have been resolved for an ABCE1 mutant lacking the FeS cluster domain from Pyrococcus furiosus (pfABCE1ΔFeS, 1YQT.pdb) and from Sulfolobus solfataricus (ssABCE1ΔFeS, 3OZX.pdb) with bound ADP and Mg2+ at 1.9 and 2.0 Å resolution, respectively 19, 31. Importantly, a structure of a complete ABCE1 from Pyrococcus abyssi (paABCE1, 3BK7.pdb) was resolved to a resolution of 2.8 Å [32]. These structures have lent insights into the conserved structural elements of ABCE1.

A first snapshot of the ribosome recycling complex

A recent breakthrough in ribosome research was provided by the cryo-electron microscopy (EM) reconstruction of stalled complexes from yeast (the 80S ribosome with Dom34 and scABCE1) and P. furiosus (the 70S ribosome with aPelota and pfABCE1) at a resolution of around 7 Å [40]. These structures show that ABCE1 occupies the position of translational GTPases (eRF3/Hbs1) and is potentially capable of inducing peptide release (Figure 4). The FeS domain of ABCE1 appears to bind to the C-terminal

Allosteric control of ABCE1

Considering the biological function of ABCE1 as a ribosome splitting factor by virtue of ATP binding/hydrolysis, it seems logical that this protein would be allosterically regulated by components of the translation system, analogous to the ribosome dependence of the GTPase of class II release factors [48]. Structural evidence for allosteric regulation of translational GTPases is available for eukaryotes [44] and bacteria in a recently published crystal structure of the 70S termination complex

Ribosome recycling connects translation termination and initiation

Ribosome recycling connects two processes that have been separated in research for several decades: termination and initiation. The principles and mechanism of translation initiation and its regulation have been described in several recent reviews 49, 50, 51. The first stage of translation initiation directly results from ribosome recycling, and so provides a mechanistic link between termination and initiation.

Translation initiation begins with the formation of preinitiation complexes. In

Concluding remarks

Translation termination and ribosome recycling differ largely between the kingdoms of life. The most striking difference is the presence of the highly conserved ATPase ABCE1 in eukaryotes and archaea instead of the bacterial RRF. Besides ribosome recycling, ABCE1 is involved in several interesting cellular events. The mechanism of ribosome recycling and translation reinitiation by ABCE1 is still puzzling. To date, only the first step of ribosome recycling has been described at the structural

Acknowledgments

We thank Dr. Umar Jan and Kristin Kiosze for helpful discussions on the manuscript, and Annika Mehr for her help in the graphic layout of the figures. The German Research Foundation (SFB 902 – Molecular Mechanism of RNA-based Regulation to R.T.) supported this work.

References (97)

  • A. Karcher

    X-ray structure of RLI, an essential twin cassette ABC ATPase involved in ribosome biogenesis and HIV capsid assembly

    Structure

    (2005)
  • A. Karcher

    X-ray structure of the complete ABC enzyme ABCE1 from Pyrococcus abyssi

    J. Biol. Chem.

    (2008)
  • K.P. Hopfner et al.

    Rad50/SMC proteins and ABC transporters: unifying concepts from high-resolution structures

    Curr. Opin. Struct. Biol.

    (2003)
  • D. Barthelme

    Structural organization of essential iron-sulfur clusters in the evolutionarily highly conserved ATP-binding cassette protein ABCE1

    J. Biol. Chem.

    (2007)
  • J. Chen

    A tweezers-like motion of the ATP-binding cassette dimer in an ABC transport cycle

    Mol. Cell

    (2003)
  • S.R. Connell

    Structural basis for interaction of the ribosome with the switch regions of GTP-bound elongation factors

    Mol. Cell

    (2007)
  • E.Z. Alkalaeva

    In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3

    Cell

    (2006)
  • G.S. Allen

    The cryo-EM structure of a translation initiation complex from Escherichia coli

    Cell

    (2005)
  • C.S. Fraser

    eIF3j is located in the decoding center of the human 40S ribosomal subunit

    Mol. Cell

    (2007)
  • J.D. Gross

    Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E

    Cell

    (2003)
  • A. Marintchev

    Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation

    Cell

    (2009)
  • V.P. Pisareva

    Translation initiation on mammalian mRNAs with structured 5′UTRs requires DExH-box protein DHX29

    Cell

    (2008)
  • F.E. Paulin

    Eukaryotic translation initiation factor 5 (eIF5) acts as a classical GTPase-activator protein

    Curr. Biol.

    (2001)
  • M.G. Acker

    Kinetic analysis of late steps of eukaryotic translation initiation

    J. Mol. Biol.

    (2009)
  • F. Voigts-Hoffmann

    Structural insights into eukaryotic ribosomes and the initiation of translation

    Curr. Opin. Struct. Biol.

    (2012)
  • M. Graille

    Structure of yeast Dom34: a protein related to translation termination factor Erf1 and involved in No-Go decay

    J. Biol. Chem.

    (2008)
  • A.V. Zavialov

    Release of peptide promoted by the GGQ motif of class 1 release factors regulates the GTPase activity of RF3

    Mol. Cell

    (2002)
  • A.V. Zavialov

    A posttermination ribosomal complex is the guanine nucleotide exchange factor for peptide release factor RF3

    Cell

    (2001)
  • H. Fan-Minogue

    Distinct eRF3 requirements suggest alternate eRF1 conformations mediate peptide release during eukaryotic translation termination

    Mol. Cell

    (2008)
  • A.V. Zavialov

    Splitting of the posttermination ribosome into subunits by the concerted action of RRF and EF-G

    Mol. Cell

    (2005)
  • G. Hirokawa

    The ribosome-recycling step: consensus or controversy?

    Trends Biochem. Sci.

    (2006)
  • F. Peske

    Sequence of steps in ribosome recycling as defined by kinetic analysis

    Mol. Cell

    (2005)
  • C. Bisbal

    Cloning and characterization of a RNAse L inhibitor. A new component of the interferon-regulated 2-5A pathway

    J. Biol. Chem.

    (1995)
  • V. Shyamala

    Structure-function analysis of the histidine permease and comparison with cystic fibrosis mutations

    J. Biol. Chem.

    (1991)
  • S. Schutz et al.

    Getting ready to commit: ribosomes rehearse translation

    Nat. Struct. Mol. Biol.

    (2012)
  • C.J. Shoemaker et al.

    Translation drives mRNA quality control

    Nat. Struct. Mol. Biol.

    (2012)
  • S. Kervestin et al.

    NMD: a multifaceted response to premature translational termination

    Nat. Rev. Mol. Cell Biol.

    (2012)
  • V.P. Pisareva

    Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes

    EMBO J.

    (2011)
  • C.J. Shoemaker et al.

    Kinetic analysis reveals the ordered coupling of translation termination and ribosome recycling in yeast

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

    (2011)
  • T. Fujiwara

    Ribosome recycling factor disassembles the post-termination ribosomal complex independent of the ribosomal translocase activity of elongation factor G

    Mol. Microbiol.

    (2004)
  • M.K. Doma et al.

    Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation

    Nature

    (2006)
  • P.A. Frischmeyer

    An mRNA surveillance mechanism that eliminates transcripts lacking termination codons

    Science

    (2002)
  • A. van Hoof

    Exosome-mediated recognition and degradation of mRNAs lacking a termination codon

    Science

    (2002)
  • G.C. Atkinson

    Evolution of nonstop, no-go and nonsense-mediated mRNA decay and their termination factor-derived components

    BMC Evol. Biol.

    (2008)
  • C.J. Shoemaker

    Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay

    Science

    (2010)
  • K. Kobayashi

    Structural basis for mRNA surveillance by archaeal Pelota and GTP-bound EF1alpha complex

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

    (2010)
  • D. Barthelme

    Ribosome recycling depends on a mechanistic link between the FeS cluster domain and a conformational switch of the twin-ATPase ABCE1

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

    (2011)
  • C.M. Coelho

    Growth and cell survival are unevenly impaired in pixie mutant wing discs

    Development

    (2005)
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