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

Nature structural & molecular biology · 2016 · Vol. 23 (12) · pp. 1101-1110

Abstract

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.

Publication Types

["Journal Article"]

Keywords

[]

MeSH Terms

["3' Untranslated Regions", "Alternative Splicing", "Cell Line", "Cytomegalovirus", "Cytomegalovirus Infections", "Gene Expression Regulation", "Host-Pathogen Interactions", "Humans", "Polyadenylation", "RNA, Messenger", "RNA, Viral", "Transcription Factors", "Transcriptome", "Up-Regulation", "mRNA Cleavage and Polyadenylation Factors"]

Funding

R01 HG004659 NHGRI NIH HHS (United States)
P30 CA023100 NCI NIH HHS (United States)
T32 GM008666 NIGMS NIH HHS (United States)
U54 HG007005 NHGRI NIH HHS (United States)
R01 NS075449 NINDS NIH HHS (United States)

Linked Datasets (4)

GSE73843 GSE via ncbi_elink
GEO

Transcriptome analysis of diverse cell types infected with human cytomegalovirus [array]

Homo sapiens
GSE74250 GSE via ncbi_elink
GEO

Transcriptome analysis of diverse cell types infected with human cytomegalovirus

Homo sapiens
GSE73853 GSE via ncbi_elink
GEO

Transcriptome analysis of diverse cell types infected with human cytomegalovirus [RNA-Seq]

Homo sapiens
26 data files
FileTypeSize
EC_InfectedHCMVTB40E_48h.fastq.gz RNA-Seq 10.5 GB
EC_InfectedHCMVTB40E_48h.fastq.gz RNA-Seq 10.5 GB
EC_InfectedHCMVTB40E_96h.fastq.gz RNA-Seq 12.8 GB
EC_InfectedHCMVTB40E_96h.fastq.gz RNA-Seq 12.8 GB
EC_Mock_48h.fastq.gz RNA-Seq 10.1 GB
EC_Mock_48h.fastq.gz RNA-Seq 10.1 GB
HFF_InfectedHCMVTB40E_48h.fastq.gz RNA-Seq 11.7 GB
HFF_InfectedHCMVTB40E_48h.fastq.gz RNA-Seq 11.7 GB
HFF_InfectedHCMVTB40E_96h.fastq.gz RNA-Seq 11.0 GB
HFF_InfectedHCMVTB40E_96h.fastq.gz RNA-Seq 11.0 GB
HFF_InfectedHSV2_8h.fastq.gz RNA-Seq 1.3 GB
HFF_InfectedHSV2_8h.fastq.gz RNA-Seq 1.3 GB
HFF_Mock_48h.fastq.gz RNA-Seq 7.7 GB
HFF_Mock_48h.fastq.gz RNA-Seq 7.7 GB
HFF_MockforHSV_8h.fastq.gz RNA-Seq 1.6 GB
HFF_MockforHSV_8h.fastq.gz RNA-Seq 1.6 GB
NPC_InfectedHCMVTB40E_48h.fastq.gz RNA-Seq 13.6 GB
NPC_InfectedHCMVTB40E_48h.fastq.gz RNA-Seq 13.6 GB
NPC_InfectedHCMVTB40E_96h.fastq.gz RNA-Seq 12.4 GB
NPC_InfectedHCMVTB40E_96h.fastq.gz RNA-Seq 12.4 GB
NPC_Mock_48h.fastq.gz RNA-Seq 13.5 GB
NPC_Mock_48h.fastq.gz RNA-Seq 13.5 GB
Tcell_Control_5d.fastq.gz RNA-Seq 7.2 GB
Tcell_Control_5d.fastq.gz RNA-Seq 7.2 GB
Tcell_InfectedHIV1_5d.fastq.gz RNA-Seq 8.8 GB
Tcell_InfectedHIV1_5d.fastq.gz RNA-Seq 8.8 GB
GSE86791 GSE via ncbi_elink
GEO

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

Homo sapiens
18 data files
FileTypeSize
CPEB1_OE1_R1_001.fastq.gz RNA-Seq 5.0 GB
CPEB1_OE1_R1_001.fastq.gz RNA-Seq 5.0 GB
CPEB1_OE2_R1_001.fastq.gz RNA-Seq 2.1 GB
CPEB1_OE2_R1_001.fastq.gz RNA-Seq 2.1 GB
GFP_OE_R1_001.fastq.gz RNA-Seq 5.6 GB
GFP_OE_R1_001.fastq.gz RNA-Seq 5.6 GB
HCMV_R1_001.fastq.gz RNA-Seq 5.8 GB
HCMV_R1_001.fastq.gz RNA-Seq 5.8 GB
infCPEB1_R3.fastq.gz OTHER 122.2 MB
infCPEB1_R3.fastq.gz OTHER 122.2 MB
inf_R3.fastq.gz OTHER 96.5 MB
inf_R3.fastq.gz OTHER 96.5 MB
Mock_R1_001.fastq.gz RNA-Seq 4.8 GB
Mock_R1_001.fastq.gz RNA-Seq 4.8 GB
siCPEB1_R1_001.fastq.gz RNA-Seq 4.2 GB
siCPEB1_R1_001.fastq.gz RNA-Seq 4.2 GB
uninf_R3.fastq.gz OTHER 102.6 MB
uninf_R3.fastq.gz OTHER 102.6 MB

Analysis Pipelines (4)

Microarray geo_data_processing GSE73843
RNA-seq geo_data_processing GSE73853
Microarray geo_data_processing GSE74250
RNA-seq geo_data_processing GSE86791