Modulation of enteroviral proteinase cleavage of poly(A)-binding protein (PABP) by conformation and PABP-associated factors

Rivera, Carlos I.; Lloyd, Richard E.

doi:10.1016/j.virol.2008.02.002

Cited by 30 publications

(27 citation statements)

References 51 publications

(77 reference statements)

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“…Also, as in vivo, PABP cleavage in the reactions never proceeded to completion, though 3C pro cleaved another cellular protein, G3BP, to completion in 10 minutes (not shown) (51). In contrast, the cleavage of eIF4G by recombinant coxsackievirus B3 2A pro in these reactions was rapid and profound (Fig.…”

Section: Kinetics Of Cleavage Of Eif4g Pabp and Itafs In Hela Transmentioning

confidence: 78%

“…We have shown previously that PV 3C pro preferentially cleaves PABP associated with actively translating polysomes and that these cleavage events, as opposed to cleavage by 2A pro , are determinants for the host cell translation shutoff seen in infection (39). We have also shown that PABP cleavage by viral proteases is regulated by PABP adopting multiple stable conformations and interactions with some PABP-binding proteins and that 3CD precursor and 3C pro cleave PABP with equivalent efficiency and cleavage site preference (51).…”

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confidence: 83%

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Cleavage of Poly(A)-Binding Protein by Poliovirus 3C Proteinase Inhibits Viral Internal Ribosome Entry Site-Mediated Translation

Bonderoff

LaRey

Lloyd³

2008

J Virol

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Poliovirus (PV) is a medically important member of the picornavirus genus Enterovirus, which is collectively responsible for millions of human infections per year worldwide. Enteroviruses contain a single-stranded RNA genome that is a direct template for translation by the host cell's translational machinery, and this translation step is required for host morbidity and progeny virus production. The ϳ7.5-kb PV genome is comprised of a single open reading frame encoding a 247-kDa polyprotein which is processed to 11 final products, a short 3Ј untranslated region (UTR) with defined RNA structure, a poly(A) tail of strain-specific length that is approximately 80 to 120 nucleotides long, and a ϳ700-nucleotide 5Ј UTR containing an internal ribosome entry site (IRES) for facilitation of viral translation. The extreme 5Ј end of the PV genome, known as the cloverleaf or oriL, has roles in nucleic acid stability (5), translation (54), and viral genomic RNA replication (43,59). Notably, the viral genome has no 7-methylguanosine cap.The viral IRES is responsible for driving translation, and the 7-methylguanosine cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is not required for IRES-dependent translation. The large scaffolding protein eIF4G is cleaved early in PV infection, and the fragments produced cannot support capdependent translation (40); however, cleaved eIF4G stimulates IRES-driven translation more than intact eIF4G (12,25,41). The PV IRES is thought to bind eIF4G directly, as it does to related viral IRESs such as that of encephalomyocarditis virus (34). The C-terminal fragment of eIF4G that functions in IRES-dependent translation (p100) is able to recruit eIF3 and the 40S ribosomal subunit to the viral RNA. Other canonical translation factors involved in PV IRES-mediated translation include the DEAD box helicase eIF4A and its activator eIF4B, which also directly binds the IRES (47). The poly(A) tail/ poly(A)-binding protein (PABP) interaction with eIF4G is also proposed to stimulate PV IRES translation by mediating a closed-loop structure and enhanced interactions between PABP and eIF4GI (7,13,45,57).In addition to these canonical translation factors, other cellular proteins, IRES trans-activating factors (ITAFs), stimulate IRES translation. These include polypyrimidine tract-binding protein (PTB) (26, 50), poly r(C)-binding protein 2 (PCBP2) (9, 10), lupus autoantigen (La) (44), and upstream of N-ras (Unr) (16). The ITAFs map to multiple binding sites in enteroviral IRES structures (9,18,23) and are proposed to have roles as chaperones to hold the IRES in a translation-competent conformation and possibly to also act as de facto signals for the switch from translation to replication. Additionally, ITAFs may recruit effector proteins to the IRES, as seen in the recent discovery that SRp20 binds PCBP2 and is required for IRES-mediated translation (6).The two viral proteinases, 2A proteinase (2A pro ) and 3C proteinase (3C pro ), cleave several cellular proteins during infection in addition to viral p...

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Section: Kinetics Of Cleavage Of Eif4g Pabp and Itafs In Hela Transmentioning

confidence: 78%

mentioning

confidence: 83%

Cleavage of Poly(A)-Binding Protein by Poliovirus 3C Proteinase Inhibits Viral Internal Ribosome Entry Site-Mediated Translation

Bonderoff

LaRey

Lloyd³

2008

J Virol

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“…Numerous studies have indicated that viral machinery induces host translational shutoff by altering the cellular distribution (4,(23)(24)(25)(26)(27)(28)(29) or specific cleavage (30)(31)(32)(33)(34)(35)(36)(37)(38) of the PABPC1 protein. The redistribution of PABPC1 to the nucleus is accompanied by a reduction in global protein synthesis but is not linked to apoptosis (18).…”

mentioning

confidence: 99%

Interplay between Polyadenylate-Binding Protein 1 and Kaposi's Sarcoma-Associated Herpesvirus ORF57 in Accumulation of Polyadenylated Nuclear RNA, a Viral Long Noncoding RNA

Massimelli

Majerčiak

Kruhlak

et al. 2013

J Virol

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Polyadenylate-binding protein cytoplasmic 1 (PABPC1) is a cytoplasmic-nuclear shuttling protein important for protein translation initiation and both RNA processing and stability. We report that PABPC1 forms a complex with the Kaposi's sarcomaassociated herpesvirus (KSHV) ORF57 protein, which allows ORF57 to interact with a 9-nucleotide (nt) core element of KSHV polyadenylated nuclear (PAN) RNA, a viral long noncoding RNA (lncRNA), and increase PAN stability. The N-terminal RNA recognition motifs (RRMs) of PABPC1 are necessary for the direct interaction with ORF57. During KSHV lytic infection, the expression of viral ORF57 leads to a substantial decrease in overall PABPC1 expression, along with a shift in the cellular distribution of the remaining PABPC1 to the nucleus. Interestingly, PABPC1 and ORF57 have opposing functions in modulating PAN steady-state accumulation. The suppressive effect of PABPC1 specific to PAN expression is alleviated by small interfering RNA knockdown of PABPC1 or by overexpression of ORF57. Conversely, ectopic PABPC1 reduces ORF57 steady-state protein levels and induces aberrant polyadenylation of PAN and thereby indirectly inhibits ORF57-mediated PAN accumulation. However, E1B-AP5 (heterogeneous nuclear ribonucleoprotein U-like 1), which interacts with a region outside the 9-nt core to stimulate PAN expression, does not interact or even colocalize with ORF57. Unlike PABPC1, the nuclear distribution of E1B-AP5 remains unchanged by viral lytic infection or overexpression of ORF57. Together, these data indicate that PABPC1 is an important cellular target of viral ORF57 to directly upregulate PAN accumulation during viral lytic infection, and the ability of host PABPC1 to disrupt ORF57 expression is a strategic host counterbalancing mechanism.

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“…pro is responsible for polysome-associated PABP cleavage, which appears to be responsible for synergistic inhibition of cap-dependent translation (9,18,35). 2A…”

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confidence: 99%

Viable Polioviruses That Encode 2A Proteins with Fluorescent Protein Tags

Teterina

Levenson

Ehrenfeld

2010

J Virol

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Modulation of enteroviral proteinase cleavage of poly(A)-binding protein (PABP) by conformation and PABP-associated factors

Cited by 30 publications

References 51 publications

Cleavage of Poly(A)-Binding Protein by Poliovirus 3C Proteinase Inhibits Viral Internal Ribosome Entry Site-Mediated Translation

Cleavage of Poly(A)-Binding Protein by Poliovirus 3C Proteinase Inhibits Viral Internal Ribosome Entry Site-Mediated Translation

Interplay between Polyadenylate-Binding Protein 1 and Kaposi's Sarcoma-Associated Herpesvirus ORF57 in Accumulation of Polyadenylated Nuclear RNA, a Viral Long Noncoding RNA

Viable Polioviruses That Encode 2A Proteins with Fluorescent Protein Tags

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