A novel function for human factor C1 (HCF-1), a host protein required for herpes simplex virus infection, in pre-mRNA splicing

Paul Ajuh, Janet Chusainow, Ursula Ryder, Angus I. Lamond

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Human factor C1 (HCF-1) is needed for the expression of herpes simplex virus 1 (HSV-1) immediate-early genes in infected mammalian cells. Here, we provide evidence that HCF-1 is required for spliceosome assembly and splicing in mammalian nuclear extracts. HCF-1 interacts with complexes containing splicing snRNPs in uninfected mammalian cells and is a stable component of the spliceosome complex. We show that a missense mutation in HCF-1 in the BHK21 hamster cell line tsBN67, at the non-permissive temperature, inhibits the protein's interaction with U1 and U5 splicing snRNPs, causes inefficient spliceosome assembly and inhibits splicing. Transient expression of wild-type HCF-1 in tsBN67 cells restores splicing at the non-permissive temperature. The inhibition of splicing in tsBN67 cells correlates with the temperature-sensitive cell cycle arrest phenotype, suggesting that HCF-1-dependent splicing events may be required for cell cycle progression.

Original languageEnglish
Pages (from-to)6590-6602
Number of pages13
JournalEMBO Journal
Volume21
Issue number23
DOIs
Publication statusPublished - 1 Dec 2002

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Keywords

  • Factor C1
  • HCF-1
  • HSV
  • Pre-mRNA splicing
  • Spliceosome

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