Dataset Information

Thriving under stress: selective translation of HIV-1 structural protein mRNA during Vpr-mediated impairment of eIF4E translation activity.

ABSTRACT: Translation is a regulated process and is pivotal to proper cell growth and homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis and thus may be susceptible to its perturbation in response to stress, co-infection, and/or cell cycle arrest. HIV-1 infection arrests the cell cycle in the G2/M phase, potentially disrupting the regulation of host cell translation. In this study, we present evidence that HIV-1 infection downregulates translation in lymphocytes, attributable to the cell cycle arrest induced by the HIV-1 accessory protein Vpr. The molecular basis of the translation suppression is reduced accumulation of the active form of the translation initiation factor 4E (eIF4E). However, synthesis of viral structural proteins is sustained despite the general suppression of protein production. HIV-1 mRNA translation is sustained due to the distinct composition of the HIV-1 ribonucleoprotein complexes. RNA-coimmunoprecipitation assays determined that the HIV-1 unspliced and singly spliced transcripts are predominantly associated with nuclear cap binding protein 80 (CBP80) in contrast to completely-spliced viral and cellular mRNAs that are associated with eIF4E. The active translation of the nuclear cap binding complex (CBC)-bound viral mRNAs is demonstrated by ribosomal RNA profile analyses. Thus, our findings have uncovered that the maintenance of CBC association is a novel mechanism used by HIV-1 to bypass downregulation of eIF4E activity and sustain viral protein synthesis. We speculate that a subset of CBP80-bound cellular mRNAs contribute to recovery from significant cellular stress, including human retrovirus infection.

SUBMITTER: Sharma A

PROVIDER: S-EPMC3310836 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Thriving under stress: selective translation of HIV-1 structural protein mRNA during Vpr-mediated impairment of eIF4E translation activity.

Sharma Amit A Yilmaz Alper A Marsh Kim K Cochrane Alan A Boris-Lawrie Kathleen K

PLoS pathogens 20120322 3

Translation is a regulated process and is pivotal to proper cell growth and homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis and thus may be susceptible to its perturbation in response to stress, co-infection, and/or cell cycle arrest. HIV-1 infection arrests the cell cycle in the G2/M phase, potentially disrupting the regulation of host cell translation. In this study, we present evidence that HIV-1 infection downregulates translation in lymphoc ...[more]

PMID: 22457629

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Project description:The reprogramming of gene expression is one of the key responses to environmental stimuli, whereas changes in mRNA do not necessarily bring forth corresponding changes of the protein, which seems partially due to the stress-induced selective translation. To address this issue, we systematically compared the transcriptome and translatome using self-produced and publicly available datasets to decipher how and to what extent the coordination and discordance between transcription and translation came to be in response to wounding (self-produced), dark to light transition, heat, hypoxia, Pi starvation and the pathogen-associated molecular pattern (elf18) in Arabidopsis. We found that changes in total mRNAs (transcriptome) and ribosome-protected fragments (translatome) are highly correlated upon dark to light transition or heat stress. However, this close correlation was generally lost under other four stresses analyzed in this study, especially during immune response, which suggests that transcription and translation are differentially coordinated under distinct stress conditions. Moreover, Gene Ontology (GO) enrichment analysis showed that typical stress responsive genes were upregulated at both transcriptional and translational levels, while non-stress-specific responsive genes were changed solely at either level or downregulated at both levels. Taking wounding responsive genes for example, typical stress responsive genes are generally involved in functional categories related to dealing with the deleterious effects caused by the imposed wounding stress, such as response to wounding, response to water deprivation and response to jasmonic acid, whereas non-stress-specific responsive genes are often enriched in functional categories like S-glycoside biosynthetic process, photosynthesis and DNA-templated transcription. Collectively, our results revealed the differential as well as targeted coordination between transcriptome and translatome in response to diverse stresses, thus suggesting a potential model wherein preferential ribosome loading onto the stress-upregulated mRNA pool could be a pacing factor for selective translation.

Dataset Information

Thriving under stress: selective translation of HIV-1 structural protein mRNA during Vpr-mediated impairment of eIF4E translation activity.

Publications

Thriving under stress: selective translation of HIV-1 structural protein mRNA during Vpr-mediated impairment of eIF4E translation activity.

Similar Datasets

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