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Nat Struct Mol Biol ; 23(12): 1101-1110, 2016 12.
Article in English | MEDLINE | ID: mdl-27775709

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.


Subject(s)
Cytomegalovirus Infections/genetics , Cytomegalovirus/genetics , RNA, Messenger/genetics , RNA, Viral/genetics , Transcription Factors/genetics , Transcriptome , mRNA Cleavage and Polyadenylation Factors/genetics , 3' Untranslated Regions , Alternative Splicing , Cell Line , Cytomegalovirus/physiology , Cytomegalovirus Infections/metabolism , Cytomegalovirus Infections/pathology , Cytomegalovirus Infections/virology , Gene Expression Regulation , Host-Pathogen Interactions , Humans , Polyadenylation , Transcription Factors/metabolism , Up-Regulation , mRNA Cleavage and Polyadenylation Factors/metabolism
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