The GTP-binding Release Factor eRF3 as a Key Mediator Coupling Translation Termination to mRNA Decay

Kobayashi, Tetsuo; Funakoshi, Yuji; Hoshino, Shin‐ichi; Katada, Toshiaki

doi:10.1074/jbc.m405163200

Cited by 60 publications

(68 citation statements)

References 44 publications

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“…Importantly, the binding of eRF3 to eRF1 does not shield the subdomain of domain C (residues 338-381; human numbering) that has been implicated in PP2A binding (Andjelkovic et al 1996), suggesting that eRF1 may also use this subdomain to associate with other proteins regulating translation termination (e.g., Upf1). Domain M of eRF1 enhances the overall affinity between eRF1 and eRF3 (Kononenko et al 2008), and under certain conditions, the interaction between eRF1 and eRF3 requires the presence of GTP (Kobayashi et al 2004;Ivanov et al 2008). These observations are in agreement with our modeling and SAXS analysis, which predict a direct interaction between domain M of eRF1 and the GTPase domain of eRF3 in the presence of GTP.…”

Section: Discussionmentioning

confidence: 99%

Structural insights into eRF3 and stop codon recognition by eRF1

Chen¹,

Saito²,

Pisarev³

et al. 2009

Genes Dev.

145

261

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Eukaryotic translation termination is mediated by two interacting release factors, eRF1 and eRF3, which act cooperatively to ensure efficient stop codon recognition and fast polypeptide release. The crystal structures of human and Schizosaccharomyces pombe full-length eRF1 in complex with eRF3 lacking the GTPase domain revealed details of the interaction between these two factors and marked conformational changes in eRF1 that occur upon binding to eRF3, leading eRF1 to resemble a tRNA molecule. Small-angle X-ray scattering analysis of the eRF1/eRF3/GTP complex suggested that eRF1's M domain contacts eRF3's GTPase domain. Consistently, mutation of Arg192, which is predicted to come in close contact with the switch regions of eRF3, revealed its important role for eRF1's stimulatory effect on eRF3's GTPase activity. An ATP molecule used as a crystallization additive was bound in eRF1's putative decoding area. Mutational analysis of the ATP-binding site shed light on the mechanism of stop codon recognition by eRF1.[Keywords: eRF1; eRF3; protein biosynthesis; stop codon recognition; translation termination; translational GTPase] Supplemental material is available at http://www.genesdev.org.

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Section: Discussionmentioning

confidence: 99%

Structural insights into eRF3 and stop codon recognition by eRF1

Chen¹,

Saito²,

Pisarev³

et al. 2009

Genes Dev.

145

261

View full text Add to dashboard Cite

show abstract

“…We further investigated the interaction between Upf1 and eRF3 in upf1D cells, since Upf1 interacts with the release factors, eRF1 and eRF3, to regulate the translation termination efficiency (Czaplinski et al 1998;Kobayashi et al 2004). As shown in Figure 5D, the interaction between Upf1 and eRF3 was not affected by the deletion of the CH domain or its mutations (Fig.…”

Section: E3 Ubiquitin Ligase Activity Of Ring-related Upf1 Requires Imentioning

confidence: 94%

Upf1 potentially serves as a RING-related E3 ubiquitin ligase via its association with Upf3 in yeast

Takahashi¹,

Araki²,

Ohya³

et al. 2008

RNA

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Three Upf proteins are essential to the nonsense-mediated mRNA decay (NMD) pathway. Although these proteins assemble on polysomes for recognition of aberrant mRNAs containing premature termination codons, the significance of this assembly remains to be elucidated. The Cys-and His-rich repeated N terminus (CH domain) of Upf1 has been implicated in its binding to Upf2. Here, we show that CH domain also plays a RING-related role for Upf1 to exhibit E3 ubiquitin ligase activity in yeast. Despite the sequence divergence from typical E3-RING fingers, the CH domain of yeast Upf1 specifically and directly interacted with the yeast E2 Ubc3. Interestingly, Upf1 served as a substrate for the in vitro self-ubiquitination, and the modification required its association with Upf3 rather than Upf2. Substitution of the coordinated Cys and His residues in the CH domain impaired not only self-ubiquitination of Upf1 but also rapid decay of aberrant mRNAs. These results suggest that Upf1 may serve as an E3 ubiquitin ligase upon its association with Upf3 and play an important role in signaling to the NMD pathway.

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“…Indeed, termination efficiency can be affected by interaction between eRF3, a component of the termination complex, and the poly(A)-binding protein (Amrani et al 2004;Kobayashi et al 2004), and thus by separating the two, long 39 UTRs might decrease termination efficiency.…”

Section: Long Readthrough Transcripts and Predicted Sequence Motifs Smentioning

confidence: 99%

Evidence of abundant stop codon readthrough in Drosophila and other metazoa

Jungreis¹,

Lin²,

Spokony³

et al. 2011

Genome Res.

213

298

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While translational stop codon readthrough is often used by viral genomes, it has been observed for only a handful of eukaryotic genes. We previously used comparative genomics evidence to recognize protein-coding regions in 12 species of Drosophila and showed that for 149 genes, the open reading frame following the stop codon has a protein-coding conservation signature, hinting that stop codon readthrough might be common in Drosophila. We return to this observation armed with deep RNA sequence data from the modENCODE project, an improved higher-resolution comparative genomics metric for detecting protein-coding regions, comparative sequence information from additional species, and directed experimental evidence. We report an expanded set of 283 readthrough candidates, including 16 double-readthrough candidates; these were manually curated to rule out alternatives such as A-to-I editing, alternative splicing, dicistronic translation, and selenocysteine incorporation. We report experimental evidence of translation using GFP tagging and mass spectrometry for several readthrough regions. We find that the set of readthrough candidates differs from other genes in length, composition, conservation, stop codon context, and in some cases, conserved stem-loops, providing clues about readthrough regulation and potential mechanisms. Lastly, we expand our studies beyond Drosophila and find evidence of abundant readthrough in several other insect species and one crustacean, and several readthrough candidates in nematode and human, suggesting that functionally important translational stop codon readthrough is significantly more prevalent in Metazoa than previously recognized.

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The GTP-binding Release Factor eRF3 as a Key Mediator Coupling Translation Termination to mRNA Decay

Cited by 60 publications

References 44 publications

Structural insights into eRF3 and stop codon recognition by eRF1

Structural insights into eRF3 and stop codon recognition by eRF1

Upf1 potentially serves as a RING-related E3 ubiquitin ligase via its association with Upf3 in yeast

Evidence of abundant stop codon readthrough in Drosophila and other metazoa

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