| 1. |
- Dufva, Martin, 1967, et al.
(författare)
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Epstein-Barr virus nuclear antigen 5 inhibits pre-mRNA cleavage and polyadenylation.
- 2002
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Ingår i: Nucleic acids research. - 1362-4962. ; 30:10, s. 2131-43
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Tidskriftsartikel (refereegranskat)abstract
- The long-standing suspicion that Epstein-Barr virus nuclear antigen 5 (EBNA5) is involved in transcription regulation was recently confirmed by the observation by several groups that EBNA5 cooperates with EBNA2 in activation of the LMP1 promoter. In attempts to elucidate the molecular basis for the EBNA5-mediated enhancement of EBNA2 transactivation, we obtained evidence of an additional function of EBNA5: at high but still biologically relevant levels, EBNA5 acted as a repressor of gene expression by interfering with the processing of pre-mRNA. Transient transfections with reporter plasmids revealed that EBNA5 repressed reporter mRNA and protein expression in the cytoplasm, but did not lower the steady-state level of reporter RNA in the total cellular RNA fraction. We have excluded that repression occurred as a consequence of cell death induced by EBNA5. Using the RNase protection assay with a probe comprising the pre-mRNA cleavage and polyadenylation site, EBNA5 was found to inhibit 3'-end cleavage and polyadenylation of pre-mRNAs from the reporter plasmids investigated. The effect of inhibitory levels of EBNA5 on chromosomal genes was examined in transient transfections by expression profiling using a cDNA microarray panel containing 588 genes. The results showed that EBNA5 could also inhibit the expression of chromosomal genes and did it in a discriminatory manner. This is consistent with the notion that a regulatory mechanism exists in the cell that confers specificity to the selection by EBNA5 of target genes for repression.
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| 2. |
- Rüetschi, Ulla, 1962, et al.
(författare)
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Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III.
- 2000
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Ingår i: Human genetics. - 0340-6717. ; 106:6, s. 654-62
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Tidskriftsartikel (refereegranskat)abstract
- Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPD), the second enzyme in the tyrosine catabolic pathway. The enzyme deficiency results in an accumulation and increased excretion of tyrosine and phenolic metabolites. Only a few cases with the disorder have been described, and the clinical spectrum of the disorder is unknown. Reported patients have presented with mental retardation or neurological symptoms or have been picked up by neonatal screening. We have identified four presumed pathogenic mutations (two missense and two nonsense mutations) in the HPD gene in three unrelated families encompassing four homozygous individuals and one compound heterozygous individual with tyrosinemia type III. Furthermore, a number of polymorphic mutations have been identified in the HPD gene. No correlation of the severity of the mutation and enzyme deficiency and mental function has been found; neither do the recorded tyrosine levels correlate with the clinical phenotype.
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