RNA-binding protein CPEB1 remodels host and viral RNA landscapes.
Ranjan Batra, Thomas J Stark, Alex E. Clark, Jean-Philippe Belzile, Emily C Wheeler, Brian A Yee, Hui Huang, Chelsea Gelboin-Burkhart, Stephanie C Huelga, Stefan Aigner, Brett T Roberts, Tomas J Bos, Shashank Sathe, John Paul Donohue, Frank Rigo, Manuel Ares, Deborah H Spector, Gene W Yeo
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.
Linked datasets 4
Transcriptome analysis of diverse cell types infected with human cytomegalovirus [array]
Homo sapiens
Transcriptome analysis of diverse cell types infected with human cytomegalovirus
Homo sapiens
Transcriptome analysis of diverse cell types infected with human cytomegalovirus [RNA-Seq]
Homo sapiens
26 data files
| File | Type | Size |
|---|---|---|
| EC_InfectedHCMVTB40E_48h.fastq.gz | RNA-Seq | 10.5 GB |
| EC_InfectedHCMVTB40E_96h.fastq.gz | RNA-Seq | 12.8 GB |
| EC_Mock_48h.fastq.gz | RNA-Seq | 10.1 GB |
| HFF_InfectedHCMVTB40E_48h.fastq.gz | RNA-Seq | 11.7 GB |
| HFF_InfectedHCMVTB40E_96h.fastq.gz | RNA-Seq | 11.0 GB |
| HFF_InfectedHSV2_8h.fastq.gz | RNA-Seq | 1.3 GB |
| HFF_Mock_48h.fastq.gz | RNA-Seq | 7.7 GB |
| HFF_MockforHSV_8h.fastq.gz | RNA-Seq | 1.6 GB |
| NPC_InfectedHCMVTB40E_48h.fastq.gz | RNA-Seq | 13.6 GB |
| NPC_InfectedHCMVTB40E_96h.fastq.gz | RNA-Seq | 12.4 GB |
| NPC_Mock_48h.fastq.gz | RNA-Seq | 13.5 GB |
| SRR2747462_GSM1904488 | RNA-Seq | 7.7 GB |
| SRR2747463_GSM1904489 | RNA-Seq | 11.7 GB |
| SRR2747464_GSM1904490 | RNA-Seq | 11.0 GB |
| SRR2747465_GSM1904491 | RNA-Seq | 10.1 GB |
| SRR2747466_GSM1904492 | RNA-Seq | 10.5 GB |
| SRR2747467_GSM1904493 | RNA-Seq | 12.8 GB |
| SRR2747468_GSM1904494 | RNA-Seq | 13.5 GB |
| SRR2747469_GSM1904495 | RNA-Seq | 13.6 GB |
| SRR2747470_GSM1904496 | RNA-Seq | 12.4 GB |
| SRR2747471_GSM1904497 | RNA-Seq | 1.6 GB |
| SRR2747472_GSM1904498 | RNA-Seq | 1.3 GB |
| SRR4209731_GSM2306702 | RNA-Seq | 7.2 GB |
| SRR4209732_GSM2306703 | RNA-Seq | 8.8 GB |
| Tcell_Control_5d.fastq.gz | RNA-Seq | 7.2 GB |
| Tcell_InfectedHIV1_5d.fastq.gz | RNA-Seq | 8.8 GB |
RNA binding protein CPEB1 remodels host and viral RNA landscapes [RNA-Seq]
Homo sapiens
18 data files
| File | Type | Size |
|---|---|---|
| CPEB1_OE1_R1_001.fastq.gz | RNA-Seq | 5.0 GB |
| CPEB1_OE2_R1_001.fastq.gz | RNA-Seq | 2.1 GB |
| GFP_OE_R1_001.fastq.gz | RNA-Seq | 5.6 GB |
| HCMV_R1_001.fastq.gz | RNA-Seq | 5.8 GB |
| infCPEB1_R3.fastq.gz | OTHER | 122.2 MB |
| inf_R3.fastq.gz | OTHER | 96.5 MB |
| Mock_R1_001.fastq.gz | RNA-Seq | 4.8 GB |
| siCPEB1_R1_001.fastq.gz | RNA-Seq | 4.2 GB |
| SRR4228549_GSM2308766 | RNA-Seq | 4.8 GB |
| SRR4228550_GSM2308767 | RNA-Seq | 5.8 GB |
| SRR4228551_GSM2308768 | RNA-Seq | 4.2 GB |
| SRR4228552_GSM2308769 | RNA-Seq | 5.6 GB |
| SRR4228553_GSM2308770 | RNA-Seq | 5.0 GB |
| SRR4228554_GSM2308771 | RNA-Seq | 2.1 GB |
| SRR4228555_GSM2308772 | OTHER | 102.0 MB |
| SRR4228556_GSM2308773 | OTHER | 96.0 MB |
| SRR4228557_GSM2308774 | OTHER | 122.0 MB |
| uninf_R3.fastq.gz | OTHER | 102.6 MB |
Potentially related datasets 1
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
Analysis pipelines 4
| Pipeline | Assay | Steps | Dataset |
|---|---|---|---|
| GSE73843 Microarray Data Processing geo_data_processing | Microarray | 4 | GSE73843 |
| GSE73853 RNA-seq Data Processing geo_data_processing | RNA-seq | 3 | GSE73853 |
| GSE74250 Microarray Data Processing geo_data_processing | Microarray | 4 | GSE74250 |
| GSE86791 RNA-seq Data Processing geo_data_processing | RNA-seq | 16 | GSE86791 |
Funding 5 grants
| Grant | Funder |
|---|---|
| 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) |