The yeast poly(A)-binding protein Pab1p stimulates invitro poly(A)-dependent and cap-dependent translation by distinct mechanisms

Otero, Lucy J.; Ashe, Mark P.; Sachs, Alan B.

doi:10.1093/emboj/18.11.3153

Cited by 126 publications

(136 citation statements)

References 29 publications

(77 reference statements)

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“…In addition, the effect of binding of full-length eIF4G on the cap affinity of eIF4E can be further enhanced through binding of the PABP to eIF4G (4,9,12,48). PABP can also modulate cap-dependent translation in the absence of a direct interaction with eIF4G, raising the possibility that PABP forms contacts with other factors at the 5Ј end of mRNA (30). Therefore, signaling pathways may selectively enhance eIF4GII recruitment to the cap structure either by acting directly on the eIF4GII protein or by modulating eIF4E, PABP, or other specific eIF4GII partners or even by acting on some selective PABP partners, which would strengthen eIF4G-cap interaction.…”

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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“…(89) This hypothesis is further supported by targeted mutational studies of conserved amino acids in this region. (91) Structural data is also available for the PABC domain. (92,93) This conserved sequence of 74 amino acids in length consists of five a-helices arranged in the shape of an arrow and binds specifically through a hydrophobic region to an approximately 12 amino acid peptide motif present in a number of confirmed interaction partners.…”

Section: Assembly Of the 80s Ribosomementioning

confidence: 99%

Starting the protein synthesis machine: eukaryotic translation initiation

2003

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SummaryThe final assembly of the protein synthesis machinery occurs during translation initiation. This delicate process involves both ends of eukaryotic messenger RNAs as well as multiple sequential protein-RNA and protein-protein interactions. As is expected from its critical position in the gene expression pathway between the transcriptome and the proteome, translation initiation is a selective and highly regulated process. This synopsis summarises the current status of the field and identifies intriguing open questions.

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“…One important aspect of translation initiation that might not be accommodated by the closed-loop model is the ability of PABP to stimulate the translation of nonpolyadenylated mRNAs. This regulation was first reported for a yeast system in vitro (37). Sachs and colleagues (37) defined this phenomenon as transactivation, suspecting that it is mediated by PABP that is not directly bound to mRNA.…”

Section: Discussionmentioning

confidence: 85%

“…Supporting the possibility of PABP acting in trans, PABP mutants with reduced RNA binding activity stimulated translation (37). Given that an A stretch is required for the interaction between eIF4G and PABP in yeast (10), it was suggested that a factor(s) other than eIF4G is targeted by PABP within the translation initiation complex (37). However, the PABP binding sites in yeast and mammalian eIF4G markedly differ, and the presence of poly(A) is not necessary for the human eIF4G-PABP interaction.…”

Section: Discussionmentioning

confidence: 95%

“…Sachs and colleagues (37) defined this phenomenon as transactivation, suspecting that it is mediated by PABP that is not directly bound to mRNA. Supporting the possibility of PABP acting in trans, PABP mutants with reduced RNA binding activity stimulated translation (37). Given that an A stretch is required for the interaction between eIF4G and PABP in yeast (10), it was suggested that a factor(s) other than eIF4G is targeted by PABP within the translation initiation complex (37).…”

Section: Discussionmentioning

confidence: 99%

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A mechanism of translational repression by competition of Paip2 with eIF4G for poly(A) binding protein (PABP) binding

Karim

Svitkin

Kahvejian

et al. 2006

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

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The eukaryotic mRNA 3 poly(A) tail and the 5 cap cooperate to synergistically enhance translation. This interaction is mediated by the cap-binding protein eIF4E, the poly(A) binding protein (PABP), and eIF4G, a scaffolding protein that bridges between eIF4E and PABP to bring about the circularization of the mRNA. The translational repressor, Paip2 (PABP-interacting protein 2), inhibits translation by promoting the dissociation of PABP from poly(A). Here we report on the existence of an alternative mechanism by which Paip2 inhibits translation by competing with eIF4G for binding to PABP. We demonstrate that Paip2 can abrogate the translational activity of PABP, which is tethered to the 3 end of the mRNA. Thus, Paip2 can inhibit translation by a previously unrecognized mechanism, which is independent of its ability to disrupt PABP-poly(A) interaction.circularization ͉ translation initiation T ranslational control is an important means by which cells govern gene expression. Initiation, the rate-limiting step of translation, is often the target of translational control (1). This control involves in many circumstances the cap structure at the mRNA 5Ј end and the poly(A) tail at the mRNA 3Ј end. Although both mRNA terminal structures stimulate translation on their own, their combined translational enhancement is synergistic. Such a mechanism was demonstrated in yeast, plant, and mammalian systems (2, 3) and plays a key role during development of Xenopus, Drosophila, and mouse (4). Translational synergy was also recapitulated in vitro (5-9). Hence, the cap-poly(A) tail synergy represents a common paradigm for translational control.The mechanism by which the mRNA 3Ј poly(A) tail synergizes with the 5Ј cap to stimulate translation was first documented in yeast, where PABP was shown to interact directly with the eIF4G subunit of the cap-binding complex eIF4F (see below) (10, 11). In yeast, PABP is an essential protein because deletion of the PABP1 gene is lethal (12). However, because deletion of the eIF4G binding site in PABP causes only a mild effect on yeast cell growth (13), it is not clear that PABP-eIF4G interaction is the only mechanism by which PABP regulates translation and cell growth in yeast. In addition, Searfoss et al. (14) demonstrated that yeast Ski proteins inhibit the activity of eIF5 and eIF4B in 60S ribosomal subunit joining and that this inhibition is reversed by PABP. These results implicate an important role for PABP in 60S ribosomal subunit joining. In contrast to yeast, the expression of an eIF4G mutant that does not interact with PABP in Xenopus oocytes repressed translation of polyadenylated mRNAs and inhibited progesteroneinduced oocyte maturation (15).PABP contains four RNA-recognition motifs (RRMs) and a proline-rich C-terminal region, which is N-terminal to a highly evolutionarily conserved sequence termed PABC (see below) (16,17). eIF4F is composed of the cap-binding subunit eIF4E, an RNA-dependent ATPase͞ATP-dependent RNA helicase, eIF4A, and eIF4G (reviewed in ref. 18). The latter serves...

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The yeast poly(A)-binding protein Pab1p stimulates invitro poly(A)-dependent and cap-dependent translation by distinct mechanisms

Cited by 126 publications

References 29 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

Starting the protein synthesis machine: eukaryotic translation initiation

A mechanism of translational repression by competition of Paip2 with eIF4G for poly(A) binding protein (PABP) binding

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