A new role for the cellular PABP repressor Paip2 as an innate restriction factor capable of limiting productive cytomegalovirus replication

McKinney, Caleb; Yü, Dong; Mohr, Ian

doi:10.1101/gad.221341.113

Cited by 24 publications

(25 citation statements)

References 47 publications

(84 reference statements)

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“…Both the increase in PABP and TOP mRNA translation depend upon mTORC1 activation by the HCMV multifunctional UL38 gene product, which also suppresses ER stress-induced cell death (Terhune et al, 2007; Moorman et al, 2008; Perez et al, 2011; Qian et al, 2011; McKinney et al, 2012, 2013). Furthermore, UL38 expression in uninfected cells confers TOP-like regulation on a reporter gene containing a functional 5′-TOP element (McKinney et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, the abundance of the cellular translation initiation factor eIF4F, comprised of the cap-binding subunit eIF4E and the RNA helicase eIF4A bound to eIF4G, together with the polyadenylate binding protein PABP1 increase in response to HCMV infection (Kudchodkar et al, 2004; Walsh et al, 2005; Perez et al, 2011; McKinney et al, 2012). This HCMV-induced PABP increase stimulates eIF4F assembly, virus protein accumulation, and virus replication (McKinney et al, 2012, 2013). However, how HCMV infection impacts the global repertoire of translationally-regulated cellular mRNAs and their contribution, if any, to virus biology remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Global Reprogramming of the Cellular Translational Landscape Facilitates Cytomegalovirus Replication

et al. 2014

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SUMMARY Unlike many viruses that suppress cellular protein synthesis, host mRNA translation and polyribosome formation are stimulated by human cytomegalovirus (HCMV). How HCMV impacts the translationally-regulated cellular mRNA repertoire and its contribution to virus biology remains unknown. We show using polysome profiling that HCMV presides over the cellular translational landscape, selectively accessing the host genome to extend its own coding capacity and regulate virus replication. Expression of the HCMV UL38 mTORC1-activator partially recapitulates these translational alterations in uninfected cells. The signature of cellular mRNAs translationally-stimulated by HCMV resembles pathophysiological states where translation initiation factor levels or activity increase such as cancer. In contrast, cellular mRNAs repressed by HCMV include those involved in differentiation and the immune response. Surprisingly, interfering with the virus-induced activation of cellular mRNA translation can either limit or enhance HCMV growth. The unanticipated extent to which HCMV specifically manipulates host mRNA translation may aid in understanding its association with complex inflammatory disorders and cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Global Reprogramming of the Cellular Translational Landscape Facilitates Cytomegalovirus Replication

et al. 2014

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“…For instances, circPAIP2 is derived from the gene Poly(A)-binding Protein-interacting Protein 2 (PAIP2), which has been implicated in various stress response pathways, including the regulation of Vascular Endothelial Growth Factor (VEGF) mRNA levels under hypoxic conditions (Onesto et al . 2004) and acting as an antiviral restriction factor (McKinney et al . 2013).…”

Section: Circrnas and Stressmentioning

confidence: 99%

CircRNAs: a regulator of cellular stress

Fischer

Leung

2017

Critical Reviews in Biochemistry and Molecular Biology

140

128

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Circular RNAs (CircRNAs) were first identified as a viroid and later found to also be an endogenous RNA splicing product in eukaryotes. In recent years, a series of RNA-sequencing analyses from a diverse range of eukaryotes have shed new light on these eukaryotic circRNAs, revealing dynamic expression patterns in various developmental stages and physiological conditions. In this review, we focus on circRNAs implicated in stress response pathways and explore potential mechanisms underlying their regulation. To date, circRNAs have been shown to act as scaffolds in the assembly of protein complexes, sequester proteins from native subcellular localization, activate transcription of parental genes, inhibit RNA–protein interactions, and function as regulators of microRNA activity. Although the mechanism modulating circRNA levels during stress remains unclear, circRNAs are shown to be regulated during biogenesis, degradation and exportation. As circRNAs do not have 5’ and 3’ ends, there are no entry points for exoribonucleases to initiate degradation. Such inherent stability makes this class of RNA a strong candidate to maintain homeostasis in the face of environmental challenges.

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“…We also note that this region is directly upstream of SLC23A1, a vitamin C transporter and PAIP2, a repressor of polyadenylate-binding protein PABP1. PAIP2 acts as part of innate defense against cytomegalovirus (CMV) (McKinney et al 2013), which has been detected in wild gorilla populations (Leendertz et al 2009). …”

Section: Mbementioning

confidence: 99%

Inference of Gorilla demographic and selective history from whole genome sequence data

McManus

Kelley

Song

et al. 2014

Preprint

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Although population-level genomic sequence data have been gathered extensively for humans, similar data from our closest living relatives are just beginning to emerge. Examination of genomic variation within great apes offers many opportunities to increase our understanding of the forces that have differentially shaped the evolutionary history of hominid taxa. Here, we expand upon the work of the Great Ape Genome Project by analyzing medium to high coverage whole-genome sequences from 14 western lowland gorillas (Gorilla gorilla gorilla), 2 eastern lowland gorillas (G. beringei graueri), and a single Cross River individual (G. gorilla diehli). We infer that the ancestors of western and eastern lowland gorillas diverged from a common ancestor approximately 261 ka, and that the ancestors of the Cross River population diverged from the western lowland gorilla lineage approximately 68 ka. Using a diffusion approximation approach to model the genome-wide site frequency spectrum, we infer a history of western lowland gorillas that includes an ancestral population expansion of 1.4-fold around 970 ka and a recent 5.6-fold contraction in population size 23 ka. The latter may correspond to a major reduction in African equatorial forests around the Last Glacial Maximum. We also analyze patterns of variation among western lowland gorillas to identify several genomic regions with strong signatures of recent selective sweeps. We find that processes related to taste, pancreatic and saliva secretion, sodium ion transmembrane transport, and cardiac muscle function are overrepresented in genomic regions predicted to have experienced recent positive selection.

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A new role for the cellular PABP repressor Paip2 as an innate restriction factor capable of limiting productive cytomegalovirus replication

Cited by 24 publications

References 47 publications

Global Reprogramming of the Cellular Translational Landscape Facilitates Cytomegalovirus Replication

Global Reprogramming of the Cellular Translational Landscape Facilitates Cytomegalovirus Replication

CircRNAs: a regulator of cellular stress

Inference of Gorilla demographic and selective history from whole genome sequence data

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