Nuclear accumulation of host transcripts during Zika Virus Infection
Abstract
Zika virus (ZIKV) infects fetal neural progenitor cells (NPCs) causing severe neurodevelopmental disorders in utero. Multiple pathways involved in normal brain development are dysfunctional in infected NPCs but how ZIKV centrally reprograms these pathways remains unknown. Here we show that ZIKV infection disrupts subcellular partitioning of host transcripts critical for neurodevelopment in NPCs and functionally link this process to the up-frameshift protein 1 (UPF1). UPF1 is an RNA-binding protein known to regulate decay of cellular and viral RNAs and is less expressed in ZIKV-infected cells. Using infrared crosslinking immunoprecipitation and RNA sequencing (irCLIP-Seq), we show that a subset of mRNAs loses UPF1 binding in ZIKV-infected NPCs, consistent with UPF1’s diminished expression. UPF1 target transcripts, however, are not altered in abundance but in subcellular localization, with mRNAs accumulating in the nucleus of infected or UPF1 knockdown cells. This leads to diminished protein expression of FREM2, a protein required for maintenance of NPC identity. Our results newly link UPF1 to the regulation of mRNA transport in NPCs, a process perturbed during ZIKV infection.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 05, 2023
- Source ID
- 10.1371/journal.ppat.1011070
Entities
People
- Camille R Simoneau
- Carolyn Bertozzi
- David Jimenez-Morales
- G. Renuka Kumar
- Jan E. Carette
- Julia Kaye
- Kristoffer E Leon
- Krystal A. Fontaine
- Mariah Dunlap
- Melanie Ott
- Mir M. Khalid
- Nevan J. Krogan
- Priya S. Shah
- Ryan A. Flynn
- Sakshi Tomar
- Steven Finkbeiner
- Thong T. Nguyen
Organizations
- Damon Runyon Cancer Research Foundation
- Defense Advanced Research Projects Agency
- James B. Pendleton Charitable Trust
- National Institute of Allergy and Infectious Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute on Drug Abuse
- University of California, San Francisco