Molecular Mimicry in the Decoding of Translational Stop Signals

Poole, Elizabeth S.; Askarian-Amiri, Marjan; Major, Louise L.; McCaughan, Kim K.; Scarlett, Debbie-Jane G; Wilson, Daniel N.; Tate, Warren P.

doi:10.1016/s0079-6603(03)01011-0

Cited by 23 publications

(16 citation statements)

References 98 publications

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“…resembles a slightly elongated tRNA-like molecule (Brown and Tate, 1994;Ito et al, 1996;Kisselev et al, 2003;Moffat and Tate, 1994;Nakamura and Ito, 2003;Poole et al, 2003;Song et al, 2000). As previously predicted by Frolova et al (2000), eRF1 has three discrete functions, each catalysed by separate domains of the protein (Song et al, 2000).…”

Section: Introductionmentioning

confidence: 73%

Translation termination in Arabidopsis thaliana: characterisation of three versions of release factor 1

Chapman

Brown

2004

Gene

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Section: Introductionmentioning

confidence: 73%

Translation termination in Arabidopsis thaliana: characterisation of three versions of release factor 1

Chapman

Brown

2004

Gene

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“…Translation termination ensures the formation of normalsized proteins with high fidelity and takes place when one of the three stop codons, UAA, UAG, or UGA, is translocated to the ribosomal A site where it is recognized by class-1 polypeptide release factors (RFs) that trigger hydrolysis of the ester bond between the peptidyl and tRNA moieties of peptidyl-tRNA bound to the P site (for review, see Kisselev et al 2003;Nakamura and Ito 2003;Poole et al 2003). RFs are GTPases that stimulate in vitro activity of the respective class-1 RFs and promote their release from the ribosome after peptidyl-tRNA hydrolysis (see Buckingham et al 1997;Kisselev and Buckingham 2000;Zavialov et al 2001;Alkalaeva et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Three distinct peptides from the N domain of translation termination factor eRF1 surround stop codon in the ribosome

Bulygin¹,

Khairulina²,

Kolosov³

et al. 2010

RNA

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To study positioning of the polypeptide release factor eRF1 toward a stop signal in the ribosomal decoding site, we applied photoactivatable mRNA analogs, derivatives of oligoribonucleotides. The human eRF1 peptides cross-linked to these short mRNAs were identified. Cross-linkers on the guanines at the second, third, and fourth stop signal positions modified fragment 31-33, and to lesser extent amino acids within region 121-131 (the ''YxCxxxF loop'') in the N domain. Hence, both regions are involved in the recognition of the purines. A cross-linker at the first uridine of the stop codon modifies Val66 near the NIKS loop (positions 61-64), and this region is important for recognition of the first uridine of stop codons. Since the N domain distinct regions of eRF1 are involved in a stop-codon decoding, the eRF1 decoding site is discontinuous and is not of ''protein anticodon'' type. By molecular modeling, the eRF1 molecule can be fitted to the A site proximal to the P-site-bound tRNA and to a stop codon in mRNA via a large conformational change to one of its three domains. In the simulated eRF1 conformation, the YxCxxxF motif and positions 31-33 are very close to a stop codon, which becomes also proximal to several parts of the C domain. Thus, in the A-site-bound state, the eRF1 conformation significantly differs from those in crystals and solution. The model suggested for eRF1 conformation in the ribosomal A site and cross-linking data are compatible.

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“…[1][2][3]. However, in organisms with variations in the genetic code, like ciliates, class-1 factors are able to decode only one or two stop codons with the remaining stop codon(s) reassigned to encode certain amino acids (for review, see refs.…”

mentioning

confidence: 99%

Different modes of stop codon restriction by the Stylonychia and Paramecium eRF1 translation termination factors

Lekomtsev

Kolosov

Bidou

et al. 2007

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

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In universal-code eukaryotes, a single-translation termination factor, eukaryote class-1 polypeptide release factor (eRF1), decodes the three stop codons: UAA, UAG, and UGA. In some ciliates, like Stylonychia and Paramecium, eRF1s exhibit UGA-only decoding specificity, whereas UAG and UAA are reassigned as sense codons. Because variant-code ciliates may have evolved from universalcode ancestor(s), structural features should exist in ciliate eRF1s that restrict their stop codon recognition. In omnipotent eRF1s, stop codon recognition is associated with the N-terminal domain of the protein. Using both in vitro and in vivo assays, we show here that chimeric molecules composed of the N-terminal domain of Stylonychia eRF1 fused to the core domain (MC domain) of human eRF1 retained specificity toward UGA; this unambiguously associates eRF1 stop codon specificity to the nature of its N-terminal domain. Functional analysis of eRF1 chimeras constructed by swapping ciliate N-terminal domain sequences with the matching ones from the human protein highlighted the crucial role of the tripeptide QFM in restricting Stylonychia eRF1 specificity toward UGA. Using the site-directed mutagenesis, we show that Paramecium eRF1 specificity toward UGA resides within the NIKS (amino acids 61-64) and YxCxxxF (amino acids 124 -131) motifs. Thus, we establish that eRF1 from two different ciliates relies on different molecular mechanisms to achieve specificity toward the UGA stop codon. This finding suggests that eRF1 restriction of specificity to only UGA might have been an early event occurring in independent instances in ciliate evolutionary history, possibly facilitating the reassignment of UAG and UAA to sense codons. ciliated protozoa ͉ dual gene reporter system ͉ eukaryote class-1 polypeptide release factors ͉ interdomain and intradomain protein chimeras ͉ stop codon decoding I n the universal genetic code, three stop codons (UAA, UAG, and UGA) located at the termini of mRNA sequences are decoded at the termination step of translation by class-1 polypeptide release factors (RF) (reviewed in refs. 1-3). However, in organisms with variations in the genetic code, like ciliates, class-1 factors are able to decode only one or two stop codons with the remaining stop codon(s) reassigned to encode certain amino acids (for review, see refs. 4 and 5). The molecular mechanisms that restrict stop codon recognition are entirely unknown and represent major unresolved problems in molecular biology and genetics. In eukaryotes with the standard code, a single class-1 RF, designated eukaryote class-1 polypeptide release factor (eRF1), decodes all three stop codons. Stop codon decoding results in signal transduction from the small to the large ribosomal subunit leading to cleavage of peptidyl-tRNA at the peptidyl transferase center of the ribosome.The eRF1 protein family is highly conserved and similar to archaeal class-1 RFs but differs profoundly from bacterial class-1 RFs (6-8). The only known structural element common to all class-1 RFs is a univer...

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Molecular Mimicry in the Decoding of Translational Stop Signals

Cited by 23 publications

References 98 publications

Translation termination in Arabidopsis thaliana: characterisation of three versions of release factor 1

Translation termination in Arabidopsis thaliana: characterisation of three versions of release factor 1

Three distinct peptides from the N domain of translation termination factor eRF1 surround stop codon in the ribosome

Different modes of stop codon restriction by the Stylonychia and Paramecium eRF1 translation termination factors

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