The Yeast Eukaryotic Initiation Factor 4G (eIF4G) HEAT Domain Interacts with eIF1 and eIF5 and Is Involved in Stringent AUG Selection

He, Hui; Haar, Tobias von der; Singh, Chingakham Ranjit; Miki,; Li, Bin; Hinnebusch, Alan G.; McCarthy, John E.G.; Asano, Katsura

doi:10.1128/mcb.23.15.5431-5445.2003

Cited by 88 publications

(97 citation statements)

References 41 publications

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“…eIF4G proteins contain a central region that interacts with specific RNA domains such as internal ribosomal entry sites of viral RNAs and also short motifs that exhibit general RNA-binding activities that are critical for ribosome scanning (7,22,38). Also, yeast eIF4G interacts with eIF1 and eIF5, and this interaction is required for the optimal AUG selection, indicating that yeIF4G participates in the selection of the initiation codon (14). These observations lead us to propose that eIF4GII may similarly possess selective intrinsic RNA-binding activities or may associate with specific, but still unknown, partners that contribute to the selection of particular mRNAs to be translated.…”

Section: Discussionmentioning

confidence: 99%

Selective Modification of Eukaryotic Initiation Factor 4F (eIF4F) at the Onset of Cell Differentiation: Recruitment of eIF4GII and Long-Lasting Phosphorylation of eIF4E

Caron

Charon

Cramer

et al. 2004

Molecular and Cellular Biology

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mRNA translation is mainly regulated at the level of initiation, a process that involves the synergistic action of the 5 cap structure and the 3 poly(A) tail at the ends of eukaryotic mRNA. The eukaryote initiation factor 4G(eIF4G) is a pivotal scaffold protein that forms a critical link between mRNA cap structure, poly(A) tail, and the small ribosomal subunit. There are two functional homologs of eIF4G in mammals, the original eIF4G, renamed eIF4GI, and eIF4GII that functionally complements eIF4GI. To date, biochemical and functional analysis have not identified differential activities for eIF4GI and eIF4GII. In this report, we demonstrate that eIF4GII, but not eIF4GI, is selectively recruited to capped mRNA at the onset of cell differentiation. This recruitment is coincident with a strong and long-lasting phosphorylation of eIF4E and the release of 4E-BP1, a suppressor of eIF4E function, from the cap structure, without a concomitant change in 4E-BP1's phosphorylation. Our data further indicate that cytokines such as thrombopoietin can differentially regulate eIF4GI/II activities. These results provide the first evidence that eIF4GI/II does fulfill selective roles in mammalian cells.

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Section: Discussionmentioning

confidence: 99%

Selective Modification of Eukaryotic Initiation Factor 4F (eIF4F) at the Onset of Cell Differentiation: Recruitment of eIF4GII and Long-Lasting Phosphorylation of eIF4E

Caron

Charon

Cramer

et al. 2004

Molecular and Cellular Biology

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“…Another eukaryotic translation initiation factor, eIF4GII, also contains a HEAT domain that interacts with eIF4A (40) and eIF1 and eIF5 (41). The detailed binding regions in HEAT motifs have not yet been delineated, but the loops connecting ␣A with ␣B (AB loop) may be the binding surface based on sequence conservation, mutational analysis, and oncogenic mutation studies (21).…”

Section: Discussionmentioning

confidence: 99%

Crystal Structure of Human eIF3k, the First Structure of eIF3 Subunits

Wei

Zhang

Zhou

et al. 2004

Journal of Biological Chemistry

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eIF3k, the smallest subunit of eukaryotic initiation factor 3 (eIF3), interacts with several other subunits of eIF3 and the 40 S ribosomal subunit. eIF3k is conserved among high eukaryotes, including mammals, insects, and plants, and it is ubiquitously expressed in human tissues. Interestingly, eIF3k does not exist in some species of yeast. Thus, eIF3k may play a unique regulatory role in higher organisms. Here we report the crystal structure of human eIF3k, the first high-resolution structure of an eIF3 component. This novel structure contains two distinct domains, a HEAT (named for Huntington, elongation factor 3, A subunit of protein phosphatase 2A, target of rapamycin) repeat-like HAM (HEAT analogous motif) domain and a winged-helix-like WH domain. Through structural comparison and sequence conservation analysis, we show that eIF3k has three putative protein-binding surfaces and has potential RNA binding activity. The structure provides key information for understanding the structure and function of the eIF3 complex.Translation initiation is a sophisticated cellular process, especially in eukaryotes. In general, translation initiation in eukaryotic organisms involves three steps (1); first, the methionyl-initiator tRNA (Met-tRNA i Met ) binds to the 40 S ribosomal subunit to form a 43 S preinitiation complex; second, the preinitiation complex binds to mRNA and scans to the AUG start codon in the mRNA; and third, the 60 S ribosomal subunit joins the mRNA-bound preinitiation complex to form an 80 S initiation complex, ready to commence translation. Each of these steps is stimulated by a number of proteins called eukaryotic initiation factors (eIFs).1 At least 11 eIFs have been identified, comprising over 25 polypeptides (2). In contrast, only three to five initiation factors are known in prokaryotes. This difference in protein complexity suggests that more protein-RNA and protein-protein interactions rather than RNA-RNA interactions are required for efficient translation initiation in eukaryotic cells.In mammalian cells, eIF3 is the largest initiation factor with an apparent molecular mass of about 600 kDa. It plays a central role in steps 1 and 2 of the translation initiation process (1, 3). For instance, eIF3 can bind to dissociated 40 S subunits and delay the reassociation with the 60 S ribosomal subunit for a long enough time to permit initiation. eIF3 also stabilizes the binding of the Met-tRNA i Met ⅐eIF2⅐GTP ternary complex to the 40 S subunits and promotes the formation of a 43 S preinitiation complex comprised of the 40 S subunit, the ternary complex, eIF1, eIF1A, and eIF3. In addition, eIF3 stimulates the binding of 5Ј-m 7 G-capped mRNA by interaction with the mRNA-associated factor eIF4G.eIF3 is a multisubunit protein complex. Various genes encoding eIF3 subunits have been cloned from mammals, plants, and yeasts. Twelve different subunits (eIF3a/p170, b/p116, c/p110, d/p66, e/p48, f/p47, g/p44, h/p40, i/p36, j/p45, k/p28, l/p69) have been identified in mammals, while in yeast only six subunits (eIF3...

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“…It should be noted that eIF3 binds to the corresponding region in animal eIF4G but not in yeast eIF4G (29,33,34) and as such, it would be necessary to determine which is the case for plant eIFiso4G isoforms to consider whether the observed eIFiso4G2-specific sequence changes might affect this interaction. The eIFiso4G2-specific differences are clustered together in the central region of the eIF4B interaction domain and ERVRFSREEILQHR…”

Section: --Gimkmp----mddggweiqrtrsmprgnrqtvqqpgarvqpppafnksvsvnsrllpqmentioning

confidence: 99%

Eukaryotic Initiation Factor eIFiso4G1 and eIFiso4G2 Are Isoforms Exhibiting Distinct Functional Differences in Supporting Translation in Arabidopsis

Gallie

2016

Journal of Biological Chemistry

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The eukaryotic translation initiation factor (eIF) 4G is required during protein synthesis to promote the assembly of several factors involved in the recruitment of a 40S ribosomal subunit to an mRNA. Although many eukaryotes express two eIF4G isoforms that are highly similar, the eIF4G isoforms in plants, referred to as eIF4G and eIFiso4G, are highly divergent in size, sequence, and domain organization but both can interact with eIF4A, eIF4B, eIF4E isoforms, and the poly(A)-binding protein.Nevertheless, eIF4G and eIFiso4G from wheat exhibit preferences in the mRNAs they translate optimally. For example, mRNA containing the 5-leader (called ⍀) of tobacco mosaic virus preferentially uses eIF4G in wheat germ lysate. In this study, the eIF4G isoform specificity of ⍀ was used to examine functional differences of the eIF4G isoforms in Arabidopsis. As in wheat, ⍀-mediated translation was reduced in an eif4g null mutant. Loss of the eIFiso4G1 isoform, which is similar in sequence to wheat eIFiso4G, did not substantially affect ⍀-mediated translation. However, loss of the eIFiso4G2 isoform substantially reduced ⍀-mediated translation. eIFiso4G2 is substantially divergent from eIFiso4G1 and is present only in the Brassicaceae, suggesting a recent evolution. eIFiso4G2 isoforms exhibit sequence-specific differences in regions representing partner protein and RNA binding sites. Loss of any eIF4G isoform also resulted in a substantial reduction in reporter transcript level. These results suggest that eIFiso4G2 appeared late in plant evolution and exhibits more functional similarity with eIF4G than with eIFiso4G1 during ⍀-mediated translation.The synthesis of proteins from cellular mRNAs requires several translation initiation factors that assist in recruiting the 40S ribosomal subunit to an mRNA as well as in the recognition of the initiation codon and in the assembly of the 80S ribosome (1-3). Eukaryotic initiation factor (eIF) 4F is essential to promote 40S subunit binding to an mRNA and to assist in 40S subunit scanning of the 5Ј-leader in search of the initiation codon. eIF4F is a multisubunit factor composed of eIF4E, which binds the 5Ј-cap structure; the RNA helicase, eIF4A, which unwinds the secondary structure in a 5Ј-leader that would otherwise inhibit 40S subunit scanning; and the scaffolding protein, eIF4G, which interacts with eIF4E, eIF4A, eIF4B (which stimulates the RNA helicase activity of eIF4A), eIF3 (required for 40 S binding to an mRNA), and the poly(A)-binding protein (PABP) 2 (2, 4 -6). The interactions between eIF4G and eIF4E and between eIF4G and PABP results in mRNA circularization that stimulates translation by promoting 40S subunit recruitment (7,8). An interaction between eIF4B and PABP further increases the affinity for poly(A) RNA of PABP (9 -11). These factors, therefore, are necessary for the efficient translation of most mRNAs.Although plants express two forms of eIF4G as do many eukaryotes (12), the plant isoforms are more divergent from each other than observed between eIF4G isoforms in othe...

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The Yeast Eukaryotic Initiation Factor 4G (eIF4G) HEAT Domain Interacts with eIF1 and eIF5 and Is Involved in Stringent AUG Selection

Cited by 88 publications

References 41 publications

Selective Modification of Eukaryotic Initiation Factor 4F (eIF4F) at the Onset of Cell Differentiation: Recruitment of eIF4GII and Long-Lasting Phosphorylation of eIF4E

Selective Modification of Eukaryotic Initiation Factor 4F (eIF4F) at the Onset of Cell Differentiation: Recruitment of eIF4GII and Long-Lasting Phosphorylation of eIF4E

Crystal Structure of Human eIF3k, the First Structure of eIF3 Subunits

Eukaryotic Initiation Factor eIFiso4G1 and eIFiso4G2 Are Isoforms Exhibiting Distinct Functional Differences in Supporting Translation in Arabidopsis

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