Translational Repression by a Novel Partner of Human Poly(A) Binding Protein, Paip2

Khaleghpour, Kianoush; Svitkin, Yuri V.; Craig, Andrew W.B.; DeMaria, Christine T.; Deo, Rahul C.; Burley, S.K.; Sonenberg, Nahum

doi:10.1016/s1097-2765(01)00168-x

Cited by 197 publications

(235 citation statements)

References 36 publications

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“…(85) By contrast, Paip2 is a small acidic protein that acts as a translational repressor, with a preferential effect on the translation of polyadenylated mRNAs. (87) Two molecules of Paip2 can simultaneously bind to PABP. (88) It reduces the affinity of PABP for oligo(A) and disrupts the periodicity with which multiple PABP molecules bind to poly(A).…”

Section: Assembly Of the 80s Ribosomementioning

confidence: 99%

“…4A). (87) All known PABP sequences reveal a conserved domain organisation. (89) The N-terminal part of PABP contains four highly conserved RRMs, joined together by conserved linker sequences.…”

Section: Assembly Of the 80s Ribosomementioning

confidence: 99%

“…The latter interaction displays the higher affinity and is sufficient to promote the characteristic disruption of the PABP-poly(A) complex, as well as repress translation in a poly(A)-responsive in vitro system. (87) Paip1 also has functional PAM1 (in the CTD) and PAM2 motifs (in the NTD). Paip1/PAM-1 interacts with the PABC domain and Paip1/PAM2 binds to RRM1 and RRM2 of PABP (Fig.…”

Section: Assembly Of the 80s Ribosomementioning

confidence: 99%

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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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Section: Assembly Of the 80s Ribosomementioning

confidence: 99%

Section: Assembly Of the 80s Ribosomementioning

confidence: 99%

Section: Assembly Of the 80s Ribosomementioning

confidence: 99%

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Starting the protein synthesis machine: eukaryotic translation initiation

2003

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“…Interactions between viral internal ribosomal entry site (IRES), eIF4G, PABP and the poly(A) tail are also important for picornavirus cap-independent translation. Disruption of PABP-eIF4G or PABP-poly(A) tail interactions on IRES-driven reporter mRNAs leads to reduced rates of translation (Bradrick et al, 2007;Khaleghpour et al, 2001;Michel et al, 2000;Svitkin et al, 2001). Similar results were also obtained using IRES derived from the Tobacco etch virus (Gallie, 2001;Gallie et al, 1995 , 1997) and disruption of the interaction leads to resistance (Léonard et al, 2000).…”

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confidence: 99%

Arabidopsis thaliana class II poly(A)-binding proteins are required for efficient multiplication of turnip mosaic virus

Dufresne

Ubalijoro

Fortin

et al. 2008

Journal of General Virology

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The poly(A)-binding protein (PABP) is an important translation initiation factor that binds to the polyadenylated 39 end of mRNA. We have previously shown that PABP2 interacts with the RNAdependent RNA polymerase (RdRp) and VPg-Pro of turnip mosaic virus (TuMV) within virusinduced vesicles. At least eight PABP isoforms are produced in Arabidopsis thaliana, three of which (PABP2, PABP4 and PABP8) are highly and broadly expressed and probably constitute the bulk of PABP required for cellular functions. Upon TuMV infection, an increase in protein and mRNA expression from PAB2, PAB4 and PAB8 genes was recorded. In vitro binding assays revealed that RdRp and the viral genome-linked protein (VPg-Pro) interact preferentially with PABP2 but are also capable of interaction with one or both of the other class II PABPs (i.e. PABP4 and PABP8). To assess whether PABP is required for potyvirus replication, A. thaliana single and double pab knockouts were isolated and inoculated with TuMV. All lines showed susceptibility to TuMV. However, when precise monitoring of viral RNA accumulation was performed, it was found to be reduced by 2.2-and 3.5-fold in pab2 pab4 and pab2 pab8 mutants, respectively, when compared with wild-type plants. PABP levels were most significantly reduced in the membrane-associated fraction in both of these mutants. TuMV mRNA levels thus correlated with cellular PABP concentrations in these A. thaliana knockout lines. These data provide further support for a role of PABP in potyvirus replication. INTRODUCTIONThe poly(A)-binding protein (PABP) is an abundant translation initiation factor in the cell that binds to the polyadenylated 39 end of mRNA. Its interaction with the eukaryotic translation initiation factor 4F complex (composed of the eIF4E, eIF4A and eIF4G proteins), which is bound to the 59 cap structure of the mRNA, results in the formation of a protein bridge that brings the 59 and 39 termini of the mRNA into proximity. This leads to a synergistic enhancement of translation (Sachs, 2000;Wells et al., 1998). PABP is also important for stability (BehmAnsmant et al., 2007;Parker & Song, 2004), biogenesis (Amrani et al., 1997;Brown & Sachs, 1998) and nuclear export of cellular mRNAs (Brune et al., 2005).Multiple PABP isoforms are normally found in animals and plants (Mangus et al., 2003). Eight PABP genes have been identified in Arabidopsis thaliana (Belostotsky, 2003).The corresponding proteins are divided into four classes based on gene expression and similarity. Class II genes (PAB2, PAB4 and PAB8) are highly and broadly expressed and probably encode the bulk of PABP required for cellular functions (Belostotsky, 2003).In animal cells, PABP is cleaved by proteinases of picornaviruses (Joachims et al., 1999;Kerekatte et al., 1999;Kuyumcu-Martinez et al., 2002, 2004bRodriguez Pulido et al., 2007;Zhang et al., 2007), caliciviruses (Kuyumcu-Martinez et al., 2004a) and retroviruses (Alvarez et al., 2006). The resultant cleavage leads to host translational shutdown (Joachims et al., 1999; KuyumcuMartinez ...

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“…A fragment containing PABP RRMs 1-2 strongly stimulates translation (11), most probably through its interaction with eIF4G. poly(A)-stimulated translation is controlled by two PABP-interacting proteins (Paips), Paip1 and Paip2 (28,29). Paip1 is an Ϸ70-kDa protein that stimulates translation in vivo (28).…”

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confidence: 99%

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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Translational Repression by a Novel Partner of Human Poly(A) Binding Protein, Paip2

Cited by 197 publications

References 36 publications

Starting the protein synthesis machine: eukaryotic translation initiation

Starting the protein synthesis machine: eukaryotic translation initiation

Arabidopsis thaliana class II poly(A)-binding proteins are required for efficient multiplication of turnip mosaic virus

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

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