A novel function for human factor C1 (HCF-1), a host protein required for herpes simplex virus infection, in pre-mRNA splicing.
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.
Ajuh
Paul
P
School of Life Sciences, The University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Chusainow
Janet
J
Ryder
Ursula
U
Lamond
Angus I
AI
D002467:Cell Nucleus / Q000378:metabolism; D006561:Herpes Simplex / Q000378:metabolism*; D051863:Host Cell Factor C1; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism; D014157:Transcription Factors
C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D011506:Proteins; D012333:RNA, Messenger; D017411:Ribonucleoproteins, Small Nuclear; D014157:Transcription Factors