Expression of poly(A)‐binding protein is upregulated during recovery from heat shock in HeLa cells

Ma, Shuhua; Bhattacharjee, Rumpa Biswas; Bag, Jnanankur

doi:10.1111/j.1742-4658.2008.06803.x

Cited by 37 publications

(54 citation statements)

References 40 publications

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“…It did, and additionally, transcription inhibition in the absence of infection led to PABP1 relocalization. We noted a more robust relocalization in cells that were both infected with RVFV MP12rLuc and treated with actinomycin D. As various cell stressors have been shown to lead to PABP1 relocalization, it is possible that factors related to the stress of infection also contribute to relocalization of PABP1 (41,61,62). We concluded that PABP1 relocalization is likely secondary to the NSs host transcription block.…”

Section: Discussionmentioning

confidence: 61%

Nuclear Relocalization of Polyadenylate Binding Protein during Rift Valley Fever Virus Infection Involves Expression of the NSs Gene

Copeland

Altamura

Deusen

et al. 2013

J Virol

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Rift Valley fever virus (RVFV), an ambisense member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever, an important zoonotic infection in Africa and the Middle East. Phlebovirus proteins are translated from virally transcribed mRNAs that, like host mRNA, are capped but, unlike host mRNAs, are not polyadenylated. Here, we investigated the role of PABP1 during RVFV infection of HeLa cells. Immunofluorescence studies of infected cells demonstrated a gross relocalization of PABP1 to the nucleus late in infection. Immunofluorescence microscopy studies of nuclear proteins revealed costaining between PABP1 and markers of nuclear speckles. PABP1 relocalization was sharply decreased in cells infected with a strain of RVFV lacking the gene encoding the RVFV nonstructural protein S (NSs). To determine whether PABP1 was required for RVFV infection, we measured the production of nucleocapsid protein (N) in cells transfected with small interfering RNAs (siRNAs) targeting PABP1. We found that the overall percentage of RVFV N-positive cells was not changed by siRNA treatment, indicating that PABP1 was not required for RVFV infection. However, when we analyzed populations of cells producing high versus low levels of PABP1, we found that the percentage of RVFV N-positive cells was decreased in cell populations producing physiologic levels of PABP1 and increased in cells with reduced levels of PABP1. Together, these results suggest that production of the NSs protein during RVFV infection leads to sequestration of PABP1 in the nuclear speckles, creating a state within the cell that favors viral protein production.

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Section: Discussionmentioning

confidence: 61%

Nuclear Relocalization of Polyadenylate Binding Protein during Rift Valley Fever Virus Infection Involves Expression of the NSs Gene

Copeland

Altamura

Deusen

et al. 2013

J Virol

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“…16,17 After 24 hours of Sal treatment, p-eIF2a recovered to control levels ( Figure 2B) and the polysome profile from Sal-treated cells was shifted less to the 80S fraction ( Figure 2D). During this recovery phase, the translation efficiency of g-and b-globin was increased as indicated by a significant shift to higher ribosome occupancy ( Figure 2E).…”

Section: Resultsmentioning

confidence: 98%

Induction of fetal hemoglobin through enhanced translation efficiency of γ-globin mRNA

Hahn

Lowrey

2014

Blood

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“…Increasing steady-state eIF4E, eIF4G, and PABP levels likely contribute to HCMV replication by allowing viral mRNA translation to proceed concurrently with ongoing cellular mRNA translation. Indeed, raising the initiation factor concentration is thought to enable discrete classes of mRNAs to better compete for limiting initiation factors (12,13,(18)(19)(20)22). Perhaps a similar strategy is operative in HCMV-infected cells to provide viral mRNAs better access to limiting host initiation factors.…”

Section: Discussionmentioning

confidence: 99%

Translational Control of the Abundance of Cytoplasmic Poly(A) Binding Protein in Human Cytomegalovirus-Infected Cells

Perez

McKinney

Chulunbaatar

et al. 2011

J Virol

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Irrespective of their effects on ongoing host protein synthesis, productive replication of the representative alphaherpesvirus herpes simplex virus type 1, the representative gammaherpesvirus Kaposi's sarcoma herpesvirus, and the representative betaherpesvirus human cytomegalovirus [HCMV] stimulates the assembly of the multisubunit, cap-binding translation factor eIF4F. However, only HCMV replication is associated with an increased abundance of eIF4F core components (eIF4E, eIF4G, eIF4A) and the eIF4F-associated factor poly(A) binding protein (PABP). Here, we demonstrate that the increase in translation factor concentration was readily detected in an asynchronous population of HCMV-infected primary human fibroblasts, abolished by prior UV inactivation of virus, and genetically dependent upon viral immediate-early genes. Strikingly, while increased mRNA steady-state levels accompanied the rise in eIF4E and eIF4G protein levels, the overall abundance of PABP mRNA, together with the half-life of the polypeptide it encodes, remained relatively unchanged by HCMV infection. Instead, HCMV-induced PABP accumulation resulted from new protein synthesis and was sensitive to the mTORC1-selective inhibitor rapamycin, which interferes with phosphorylation of the mTORC1 substrate p70 S6K and the translational repressor 4E-BP1. While virus-induced PABP accumulation did not require p70 S6K, it was inhibited by the expression of a dominant-acting 4E-BP1 variant unable to be inactivated by mTORC1. Finally, unlike the situation in alpha-or gammaherpesvirus-infected cells, where PABP is redistributed to nuclei, PABP accumulated in the cytoplasm of HCMV-infected cells. Thus, cytoplasmic PABP accumulation is translationally controlled in HCMV-infected cells via a mechanism requiring mTORC1-mediated inhibition of the cellular 4E-BP1 translational repressor.Herpesvirus mRNAs contain methyl-7-GTP caps and 3Ј polyadenylate tails like their host cell counterparts and are primarily translated by a cap-dependent mechanism. Assembly of the cap-binding protein eIF4E, eIF4G, and the RNA helicase eIF4A into the active, cap-binding, multisubunit translation initiation factor eIF4F represents a key step regulating translation (reviewed in reference 33). In addition to controlling small ribosome subunit recruitment to the mRNA 5Ј end, whereupon a scanning mechanism commences to locate the initiator AUG codon, eIF4F assembly is responsive to a diverse assortment of cell stress and signaling inputs, including viral infection (24). Typically, eIF4E is bound to the translational repressor 4E-BP1. Hyperphosphorylation of 4E-BP1 by activated mTORC1 relieves this repression, releasing eIF4E and exposing the binding site for eIF4G, a large assembly platform bound to eIF4A. eIF4G also binds eIF3, which directly associates with the 40S ribosome subunit. The cellular poly(A) binding protein (PABP) and the eIF4E kinase Mnk are eIF4F-associated proteins that physically associate with eIF4G and act to stimulate translation. Bound to both the 3Ј poly(A) tail and...

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Expression of poly(A)‐binding protein is upregulated during recovery from heat shock in HeLa cells

Cited by 37 publications

References 40 publications

Nuclear Relocalization of Polyadenylate Binding Protein during Rift Valley Fever Virus Infection Involves Expression of the NSs Gene

Nuclear Relocalization of Polyadenylate Binding Protein during Rift Valley Fever Virus Infection Involves Expression of the NSs Gene

Induction of fetal hemoglobin through enhanced translation efficiency of γ-globin mRNA

Translational Control of the Abundance of Cytoplasmic Poly(A) Binding Protein in Human Cytomegalovirus-Infected Cells

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