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Isolation of Cognate RNA-protein Complexes from Cells Using Oligonucleotide-directed Elution
Published on: January 16, 2017
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RNA-binding protein CPEB1 remodels host and viral RNA landscapes
Ranjan Batra1,2,3, Thomas J Stark1,2,3,4, Alex E. Clark1,4,5
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA.
Nature Structural & Molecular Biology
|November 1, 2016
Summary
Human cytomegalovirus (HCMV) infection alters host gene expression post-transcriptionally, impacting RNA splicing and poly(A)-tails. The host protein CPEB1 drives these changes and is crucial for viral replication, offering a potential therapeutic target.
Area of Science:
- Virology
- Molecular Biology
- RNA Biology
Background:
- Post-transcriptional regulation is vital for host-pathogen interactions but poorly understood.
- Human cytomegalovirus (HCMV) infection involves complex host-virus interplay at the RNA level.
Purpose of the Study:
- To investigate HCMV-induced post-transcriptional modifications in host cells.
- To identify host factors involved in these RNA processing changes.
- To explore the therapeutic potential of targeting host RNA-binding proteins in herpesvirus infections.
Main Methods:
- Comprehensive transcriptome-wide analyses of HCMV-infected cells.
- Ectopic expression and depletion of the host RNA-binding protein CPEB1.
- Analysis of alternative splicing (AS), 3' UTRs, and poly(A)-tail lengths.
- Assessment of viral titers and cytopathology.
Main Results:
- HCMV infection induces widespread AS, 3' UTR shortening, and poly(A)-tail lengthening of host transcripts.
- The host RNA-binding protein CPEB1 is upregulated by HCMV and recapitulates these changes when ectopically expressed.
- CPEB1 is essential for viral poly(A)-tail lengthening and productive HCMV infection.
- Depletion of CPEB1 reverses infection-related changes and reduces viral titers.
- Similar RNA processing alterations are observed in herpes simplex virus-2 (HSV-2) infected cells.
Conclusions:
- HCMV infection profoundly impacts host RNA processing via CPEB1.
- CPEB1 plays a critical role in both host RNA modification and viral replication.
- Targeting host RNA-binding proteins like CPEB1 represents a promising therapeutic strategy for herpesvirus infections.
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