Evolutionarily conserved non-AUG translation initiation in NAT1/p97/DAP5 (EIF4G2)

Takahashi, Kazutoshi; Maruyama, Masayoshi; Tokuzawa, Yoshimi; Murakami, Masanaka; Oda, Yasuaki; Yoshikane, Nami; Makabe, Kazuhiro W.; Ichisaka, Tomoko; Yamanaka, Shinya

doi:10.1016/j.ygeno.2004.11.012

Cited by 55 publications

(50 citation statements)

References 34 publications

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“…eIF4G (CG10811) and Ofs (CG10192) appear to be the only two eIF4G proteins encoded in the fly genome. One other candidate, l(2)01424, is more related to the proposed translational inhibitor, NAT1/p97 (Rpn1)/DAP5, than to eIF4G proteins (Takahashi et al, 2005). Although the novel N-terminus of Ofs raised the possibility that it would play a role distinct from eIF4G, our data suggest that Ofs can act as the only eIF4G in cultured cells.…”

Section: Discussionmentioning

confidence: 77%

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

et al. 2007

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During spermatogenesis, cells coordinate differentiation with the meiotic cell cycle to generate functional gametes. We identified a novel gene, which we named off-schedule (ofs), as being essential for this coordinated control. During the meiotic G 2 phase, Drosophila ofs mutant germ cells do not reach their proper size and fail to execute meiosis or significant differentiation. The accumulation of four cell cycle regulators -Cyclin A, Boule, Twine and Roughex -is altered in these mutants, indicating that ofs reveals a novel branch of the pathway controlling meiosis and differentiation. Ofs is homologous to eukaryotic translation initiation factor eIF4G. The level of ofs expression in spermatocytes is much higher than for the known eIF4G ortholog (known as eIF-4G or eIF4G), suggesting that Ofs substitutes for this protein. Consistent with this, assays for association with mRNA cap complexes, as well as RNA-interference and phenotypic-rescue experiments, demonstrate that Ofs has eIF4G activity. Based on these studies, we speculate that spermatocytes monitor G 2 growth as one means to coordinate the initiation of meiotic division and differentiation.

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Section: Discussionmentioning

confidence: 77%

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

et al. 2007

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“…These cases may represent either misannotation of the transcriptome or transcriptomic sequence or more interestingly, alternative transcription/translation events. Figure 6A shows mouse initiation factor eIF4G2, the translation of which is initiated from a GUG codon (Takahashi et al 2005). This is clearly evident in the plot, with abundant reads at the GUG followed by a continuum of reads in this frame up to the stop codon.…”

Section: Visualization Of Uorfs and Overlapping Orfs Using Riboseqrmentioning

confidence: 92%

The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis

Chung

Hardcastle

Jones

et al. 2015

RNA

119

129

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Ribosome profiling is a technique that permits genome-wide, quantitative analysis of translation and has found broad application in recent years. Here we describe a modified profiling protocol and software package designed to benefit more broadly the translation community in terms of simplicity and utility. The protocol, applicable to diverse organisms, including organelles, is based largely on previously published profiling methodologies, but uses duplex-specific nuclease (DSN) as a convenient, species-independent way to reduce rRNA contamination. We show that DSN-based depletion compares favorably with other commonly used rRNA depletion strategies and introduces little bias. The profiling protocol typically produces high levels of triplet periodicity, facilitating the detection of coding sequences, including upstream, downstream, and overlapping open reading frames (ORFs) and an alternative ribosome conformation evident during termination of protein synthesis. In addition, we provide a software package that presents a set of methods for parsing ribosomal profiling data from multiple samples, aligning reads to coding sequences, inferring alternative ORFs, and plotting average and transcript-specific aspects of the data. Methods are also provided for extracting the data in a form suitable for differential analysis of translation and translational efficiency.

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“…Matches were found to both p97a and p97b (Image 5410611 and Image 6961549). As this work was in progress, another study (Takahashi et al 2005) reported the same sequences (eIF4G2a/NAT1a and eIF4G2b/NAT1b; referred to as p97a and p97b here for consistency), which we have further analyzed here. The two zebrafish isoforms have a high homology overall with their mammalian counterparts (p97a: 82.1%; and p97b: 82.7% identity to human p97), but the caspase-3 cleavage site identified in human p97 lies in a poorly conserved loop region between two well-conserved helical elements (Bellsolell et al 2006) and is not conserved in the nonmammalian species.…”

Section: Zebrafish P97 Is Required For Early Embryonic Differentiationmentioning

confidence: 98%

“…Full-length zebrafish p97 cDNA clones were obtained from RZPD (IMAGE #5410611 for p97a/eIF4G2a/NAT1a, IMAGE #6961549 for p97b/eIF4G2b/NAT1b; as described in Takahashi et al [2005]). Linearized p97a and goosecoid plasmids were used directly as templates for in vitro transcription; the p97b sequence was first subcloned into pBluescript II KS (+/À).…”

Section: Zebrafish Developmentmentioning

confidence: 99%

The eIF4G–homolog p97 can activate translation independent of caspase cleavage

Nousch¹,

Reed²,

Bryson-Richardson³

et al. 2007

RNA

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The eukaryotic initiation factor (eIF) 4G family plays a central role during translation initiation, bridging between the 59 and 39 ends of the mRNA via its N-terminal third while recruiting other factors and ribosomes through its central and C-terminal third. The protein p97/NAT1/DAP5 is homologous to the central and C-terminal thirds of eIF4G. p97 has long been considered to be a translational repressor under normal cellular conditions. Further, caspase cleavage liberates a p86 fragment that is thought to mediate cap-independent translation in apoptotic cells. We report here that, surprisingly, human p97 is polysome associated in proliferating cells and moves to stress granules in stressed, nonapoptotic cells. Tethered-function studies in living cells show that human p97 and p86 both can activate translation; however, we were unable to detect polysome association of p86 in apoptotic cells. We further characterized the zebrafish orthologs of p97, and found both to be expressed throughout embryonic development. Their simultaneous knockdown by morpholino injection led to impaired mesoderm formation and early embryonic lethality, indicating conservation of embryonic p97 function from fish to mammals. These data indicate that fulllength p97 is a translational activator with essential role(s) in unstressed cells, suggesting a reassessment of current models of p97 function.

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Evolutionarily conserved non-AUG translation initiation in NAT1/p97/DAP5 (EIF4G2)

Cited by 55 publications

References 34 publications

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis

The eIF4G–homolog p97 can activate translation independent of caspase cleavage

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