RNA-binding protein CPEB1 remodels host and viral RNA landscapes

• DOI: 10.1038/nsmb.3310
• Publication Date: 2016-10-24T15:03:39Z
• Authors: Ranjan Batra; Thomas J Stark; Alex E. Clark; Jean-Philippe Bel...; Emily C Wheeler; Brian A Yee; Hui Huang; Chelsea Gelboin-B...; 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
• Keywords: 0301 basic medicine; Biomedical and clinical sciences; Messenger; Bioinformatics and Computational Biology; Biophysics; 610; Cytomegalovirus; Polyadenylation; Medical and Health Sciences; Article; Cell Line; 03 medical and health sciences; Genetics; 2.1 Biological and endogenous factors; 2.2 Factors relating to the physical environment; Humans; Viral; RNA, Messenger; 3' Untranslated Regions; mRNA Cleavage and Polyadenylation Factors; Biological Sciences; Up-Regulation; 3. Good health; Biological sciences; Alternative Splicing; Infectious Diseases; Chemical sciences; Gene Expression Regulation; Chemical Sciences; Cytomegalovirus Infections; Host-Pathogen Interactions; RNA; RNA, Viral; Generic health relevance; Infection; Transcriptome; Developmental Biology; Transcription Factors

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.