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RNA binding protein CPEB1 remodels host and viral RNA landscapes [RNA-Seq]

ABSTRACT: In this study, we report that HCMV infection results in widespread alternative splicing (AS), shorter 3′-untranslated regions (3′UTRs) and polyA tail lengthening in host genes and CPEB1 depletion reverses infection-related post-transcriptional changes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE86791 | GEO | 2016/09/17

SECONDARY ACCESSION(S): PRJNA342503

REPOSITORIES: GEO

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RNA-binding protein CPEB1 remodels host and viral RNA landscapes.

Project description:Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions (3' UTRs) and lengthening of poly(A)-tails in host gene transcripts. We found that the host RNA-binding protein CPEB1 was highly induced after infection, and ectopic expression of CPEB1 in noninfected cells recapitulated infection-related post-transcriptional changes. CPEB1 was also required for poly(A)-tail lengthening of viral RNAs important for productive infection. Strikingly, depletion of CPEB1 reversed infection-related cytopathology and post-transcriptional changes, and decreased productive HCMV titers. Host RNA processing was also altered in herpes simplex virus-2 (HSV-2)-infected cells, thereby indicating that this phenomenon might be a common occurrence during herpesvirus infections. We anticipate that our work may serve as a starting point for therapeutic targeting of host RNA-binding proteins in herpesvirus infections.

| S-EPMC5140759 | biostudies-literature

CPEB1 or CPEB1 (T171A, S177A) interacting proteome analysis on C2C12 cells

Project description:CPEB1 regulates cellular function by post-transcriptionally controlling its targeted transcripts' translation. After bound to CPEs, CPEB1 recruits cytoplasmic poly (A) polymerase GLD2 to elongate the poly (A) tail for the maintenance of mRNA stability. The stability of mRNA is positively correlated with translational output. It is unexamined whether CPEB1 interacts with translation machinery to regulation translation. Previous reports demonstrate that phosphorylation is required for its regulation on translation. However, it is not well understood whether phosphorylation is essential for CPEB1 interaction with translation machinery or not. Here, we performed mass spectrometry on C2 cells transfected with CPEB1-mVenus or CPEB1 (T171A, S177A)-mVenus after IgG or mVenus antibody immunoprecipitation. After analysis, we identify CPEB1 interacting proteins and the phosphorylation dependent interacting proteins such as ribosomal proteins. Thus, our data suggest that CPEB1 regulate translation by interacting with translation machinery in a phosphorylation dependent manner.

2021-11-04 | PXD020822 | Pride

CPEB1 and CPEB4-associated mRNAs in mice striatum

Project description:To identify CPEB1 and CPEB4 regulated RNA we performed CPEB1 and CPEB4 RNA immunoprecipitation (RIP) followed by microarray hybridization analysis with striatal (St) RNA from wild-type (WT) and R6/1 mice (HD mice).

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Genome-wide mRNA targets of CPEB1 in muscle stem cells

Project description:We performed CPEB1 RIP-seq on freshly isolated muscle stem cells. We found that CPEB1 associated genes are enriched in translational regulation pathways.

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The transcription and translation landscapes during human cytomegalovirus infection reveal novel host-pathogen interactions

Project description:During its long infection cycle, human cytomegalovirus (HCMV) extensively manipulates cellular gene expression to maintain conditions favorable for viral propagation. In order to reveal the signature of cellular genes that are manipulated by HCMV, we measured RNA abundance and rate of protein production through the course of HCMV infection. We characterized changes for most expressed cellular genes and although much of the regulation was transcriptional we uncover diverse and dynamic translational regulation for subsets of host genes, revealing unappreciated coordination in translational control that suggests common regulators Ribosome profiling and mRNA-seq along HCMV infection

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Expression data from Neuro2a cells treated with siRNA targeting to Cpeb1 mRNA.

Project description:Cytoplasmic polyadenylation element binding protein 1 (CPEB1) regulates polyadenylation and subsequent translation of CPE-containing mRNAs, which contributes to various physiological and pathological phenomena. To clarify changes in gene expression profiles caused by dysregulation of CPEB1 expression, we performed microarray analyses and revealed that reduced CPEB1 expression altered the expression levels of numerous genes. These findings indicate that accurate post-transcriptional regulation of CPEB1 expression contributes to the maintenance of global gene expression partially through modulating lncRNA expression.

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Project description:RNA seq of microglia from CPEB1-deficient and LPS-treated mice establish that RNA levels, splicing, and 3' poly(A) site selection are under complex regulation that mediate inflammation and phagaocytosis.

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Msi1 assists CPEB1-driven polyadenylation

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CPEB inducible knock-down in a H.D. Myz cell line

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Post-transcriptional regulation of adult CNS axonal regeneration by Cpeb1

Project description:Profiling of injury response of the localized transcriptome from wild-type and Cpeb1 knockout neurites

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