title: RNA-binding protein CPEB1 remodels host and viral RNA landscapes.
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.
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Ranjan
authors: 0000-0002-6668-2505
authors: R
authors: Batra
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.|Division of Biological Sciences, University of California at San Diego, La Jolla, California, USA.
authors: Thomas J
authors: TJ
authors: Stark
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Division of Biological Sciences, University of California at San Diego, La Jolla, California, USA.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California, USA.
authors: Alex E.
authors: AE
authors: Clark
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California, USA.
authors: Jean-Philippe
authors: JP
authors: Belzile
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Emily C
authors: EC
authors: Wheeler
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Brian A
authors: BA
authors: Yee
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Hui
authors: H
authors: Huang
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Chelsea
authors: C
authors: Gelboin-Burkhart
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Stephanie C
authors: SC
authors: Huelga
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Stefan
authors: S
authors: Aigner
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Brett T
authors: BT
authors: Roberts
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Tomas J
authors: TJ
authors: Bos
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.
authors: Shashank
authors: S
authors: Sathe
authors: RNA Center, Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, Santa Cruz, California, USA.
authors: John Paul
authors: JP
authors: Donohue
authors: Ionis Pharmaceuticals, Carlsbad, California, USA.
authors: Frank
authors: F
authors: Rigo
authors: RNA Center, Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, Santa Cruz, California, USA.
authors: Manuel
authors: 0000-0002-2552-9168
authors: M
authors: Ares
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Division of Biological Sciences, University of California at San Diego, La Jolla, California, USA.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California, USA.
authors: Deborah H
authors: DH
authors: Spector
authors: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.|Stem Cell Program, University of California at San Diego, La Jolla, California, USA.|Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA.|Molecular Engineering Laboratory, A*STAR, Singapore.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Gene W
authors: GW
authors: Yeo
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D026723:Polyadenylation; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C490386:CPEB1 protein, human; D012333:RNA, Messenger; D012367:RNA, Viral; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors