Trends in Biochemical Sciences
ReviewTying up loose ends: ribosome recycling in eukaryotes and archaea
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.
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