PMID- 27775709 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20220913 IS - 1545-9985 (Electronic) IS - 1545-9993 (Print) IS - 1545-9985 (Linking) VI - 23 IP - 12 DP - 2016 Dec TI - RNA-binding protein CPEB1 remodels host and viral RNA landscapes. PG - 1101-1110 LID - 10.1038/nsmb.3310 [doi] AB - 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. FAU - Batra, Ranjan AU - Batra R AUID- ORCID: 0000-0002-6668-2505 AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Stark, Thomas J AU - Stark TJ AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. AD - Division of Biological Sciences, University of California at San Diego, La Jolla, California, USA. FAU - Clark, Alex E AU - Clark AE AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Division of Biological Sciences, University of California at San Diego, La Jolla, California, USA. AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California, USA. FAU - Belzile, Jean-Philippe AU - Belzile JP AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California, USA. FAU - Wheeler, Emily C AU - Wheeler EC AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Yee, Brian A AU - Yee BA AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Huang, Hui AU - Huang H AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Gelboin-Burkhart, Chelsea AU - Gelboin-Burkhart C AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Huelga, Stephanie C AU - Huelga SC AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Aigner, Stefan AU - Aigner S AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Roberts, Brett T AU - Roberts BT AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Bos, Tomas J AU - Bos TJ AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Sathe, Shashank AU - Sathe S AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. FAU - Donohue, John Paul AU - Donohue JP AD - RNA Center, Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, Santa Cruz, California, USA. FAU - Rigo, Frank AU - Rigo F AD - Ionis Pharmaceuticals, Carlsbad, California, USA. FAU - Ares, Manuel Jr AU - Ares M Jr AUID- ORCID: 0000-0002-2552-9168 AD - RNA Center, Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, Santa Cruz, California, USA. FAU - Spector, Deborah H AU - Spector DH AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Division of Biological Sciences, University of California at San Diego, La Jolla, California, USA. AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California, USA. FAU - Yeo, Gene W AU - Yeo GW AD - Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA. AD - Stem Cell Program, University of California at San Diego, La Jolla, California, USA. AD - Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA. AD - Molecular Engineering Laboratory, A*STAR, Singapore. AD - Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. LA - eng GR - U54 HG007005/HG/NHGRI NIH HHS/United States GR - R01 HG004659/HG/NHGRI NIH HHS/United States GR - P30 CA023100/CA/NCI NIH HHS/United States GR - T32 GM008666/GM/NIGMS NIH HHS/United States GR - R01 NS075449/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20161024 PL - United States TA - Nat Struct Mol Biol JT - Nature structural & molecular biology JID - 101186374 RN - 0 (3' Untranslated Regions) RN - 0 (CPEB1 protein, human) RN - 0 (RNA, Messenger) RN - 0 (RNA, Viral) RN - 0 (Transcription Factors) RN - 0 (mRNA Cleavage and Polyadenylation Factors) SB - IM MH - 3' Untranslated Regions MH - Alternative Splicing MH - Cell Line MH - Cytomegalovirus/*genetics/physiology MH - Cytomegalovirus Infections/*genetics/metabolism/pathology/virology MH - Gene Expression Regulation MH - Host-Pathogen Interactions MH - Humans MH - Polyadenylation MH - RNA, Messenger/*genetics MH - RNA, Viral/*genetics MH - Transcription Factors/*genetics/metabolism MH - *Transcriptome MH - Up-Regulation MH - mRNA Cleavage and Polyadenylation Factors/*genetics/metabolism PMC - PMC5140759 MID - NIHMS819001 EDAT- 2016/11/01 06:00 MHDA- 2017/05/16 06:00 PMCR- 2017/04/24 CRDT- 2016/11/01 06:00 PHST- 2016/08/01 00:00 [received] PHST- 2016/09/22 00:00 [accepted] PHST- 2016/11/01 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/11/01 06:00 [entrez] PHST- 2017/04/24 00:00 [pmc-release] AID - nsmb.3310 [pii] AID - 10.1038/nsmb.3310 [doi] PST - ppublish SO - Nat Struct Mol Biol. 2016 Dec;23(12):1101-1110. doi: 10.1038/nsmb.3310. Epub 2016 Oct 24.