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PMID: 12456665 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 21 ·No. 23 ·2002-12-02 ·Pages 6590-602

Ajuh P, Chusainow J, Ryder U, Lamond AI

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.

MeSH Terms
Cell Nucleus/metabolism Herpes Simplex/metabolism Host Cell Factor C1 Humans In Vitro Techniques Mutation Proteins/genetics,metabolism RNA Splicing RNA, Messenger/metabolism Ribonucleoproteins, Small Nuclear/metabolism Spliceosomes/metabolism Transcription Factors
Chemicals
HCFC1 protein, human Host Cell Factor C1 Proteins RNA, Messenger Ribonucleoproteins, Small Nuclear Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ajuh Paul
School of Life Sciences, The University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Chusainow Janet
Ryder Ursula
Lamond Angus I
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2002-12-02
Pages
6590-602
Language
English
Region
England
NLM ID
8208664
PMCID
PMC136956
Subset
IM
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