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Cell phenotype-dependent splicing reflecting differential promoter usage for EBNA transcripts in EBV-carrying cells.
Gan To Kagaku Ryoho. 2000 May; 27 Suppl 2:248-60.GT

Abstract

Three types of virus-host cell interactions have been described in cells latently infected with EBV: EBNA 1 expression in type I Burkitt's lymphoma cell lines (BL), EBNA 1, LMP1 and 2 expression in most nasopharyngeal carcinomas (NPC) and EBNA 1-6 with LMP 1 and 2 expression in group III BL-lines as well as lymphoblastoid cell lines (LCL). Two group I BL lines that express only EBNA 1 were found to initiate their EBNA 1 mRNA transcription from a promoter in the Bam HI Q-fragment. They use a sequence at +210 bp relative to the Fp transcription initiation site in group I BL cell lines. The Fp promoter-region seems to be activated in the lytic cycle. LCLs initiate their transcription from one of several upstream sites, usually the Cp promoter or, less frequently, one of several Wp-promoters. Using RNA-reverse transcription polymerase chain reaction (RT-PCR), we have now shown that EBV carrying cells that do not express EBNA 2-6 always splice their EBNA mRNA at the Q-exon, while EBNA 2-6 positive cells use either the Cp or one of the Wp promotors. When EBNA 2-6 are downregulated by somatic cell hybridisation between EBNA 1-6 positive B-cell lines and non B-cells of hematopoetic, epithelial or fibroblastic origin that express the phenotype of the non-B cell parent, the parental usage of Cp/Wp is switched off, and the Q-exon is activated. NPC cells show the same pattern of promoter usage as the hybrids with non-B phenotype. Group III BL cells use both promoter regions. Thus, the virus can use two alternative programs, depending on the cell phenotype. The "EBNA-1 only" program is activated from the Q-promoter. In cells with an immunoblastic (LCL or BL group III) phenotype, the upstream Cp/Wp promoters generate a 100 kb. long pre-mRNA, from which all the EBNAs are spliced. As a rule, only one of the two programs is used for each phenotype, except for the BL group III cells that began as group I but subsequently developed into a more LCL-like cell. Such cells used both promoter regions, with or without activation of the lytic cycle.

Authors+Show Affiliations

Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. lifu.hu@mtc.ki.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10895161

Citation

Hu, L F., et al. "Cell Phenotype-dependent Splicing Reflecting Differential Promoter Usage for EBNA Transcripts in EBV-carrying Cells." Gan to Kagaku Ryoho. Cancer & Chemotherapy, vol. 27 Suppl 2, 2000, pp. 248-60.
Hu LF, Chen F, Altiok E, et al. Cell phenotype-dependent splicing reflecting differential promoter usage for EBNA transcripts in EBV-carrying cells. Gan To Kagaku Ryoho. 2000;27 Suppl 2:248-60.
Hu, L. F., Chen, F., Altiok, E., Winberg, G., Klein, G., & Ernberg, I. (2000). Cell phenotype-dependent splicing reflecting differential promoter usage for EBNA transcripts in EBV-carrying cells. Gan to Kagaku Ryoho. Cancer & Chemotherapy, 27 Suppl 2, 248-60.
Hu LF, et al. Cell Phenotype-dependent Splicing Reflecting Differential Promoter Usage for EBNA Transcripts in EBV-carrying Cells. Gan To Kagaku Ryoho. 2000;27 Suppl 2:248-60. PubMed PMID: 10895161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cell phenotype-dependent splicing reflecting differential promoter usage for EBNA transcripts in EBV-carrying cells. AU - Hu,L F, AU - Chen,F, AU - Altiok,E, AU - Winberg,G, AU - Klein,G, AU - Ernberg,I, PY - 2000/7/15/pubmed PY - 2000/8/12/medline PY - 2000/7/15/entrez SP - 248 EP - 60 JF - Gan to kagaku ryoho. Cancer & chemotherapy JO - Gan To Kagaku Ryoho VL - 27 Suppl 2 N2 - Three types of virus-host cell interactions have been described in cells latently infected with EBV: EBNA 1 expression in type I Burkitt's lymphoma cell lines (BL), EBNA 1, LMP1 and 2 expression in most nasopharyngeal carcinomas (NPC) and EBNA 1-6 with LMP 1 and 2 expression in group III BL-lines as well as lymphoblastoid cell lines (LCL). Two group I BL lines that express only EBNA 1 were found to initiate their EBNA 1 mRNA transcription from a promoter in the Bam HI Q-fragment. They use a sequence at +210 bp relative to the Fp transcription initiation site in group I BL cell lines. The Fp promoter-region seems to be activated in the lytic cycle. LCLs initiate their transcription from one of several upstream sites, usually the Cp promoter or, less frequently, one of several Wp-promoters. Using RNA-reverse transcription polymerase chain reaction (RT-PCR), we have now shown that EBV carrying cells that do not express EBNA 2-6 always splice their EBNA mRNA at the Q-exon, while EBNA 2-6 positive cells use either the Cp or one of the Wp promotors. When EBNA 2-6 are downregulated by somatic cell hybridisation between EBNA 1-6 positive B-cell lines and non B-cells of hematopoetic, epithelial or fibroblastic origin that express the phenotype of the non-B cell parent, the parental usage of Cp/Wp is switched off, and the Q-exon is activated. NPC cells show the same pattern of promoter usage as the hybrids with non-B phenotype. Group III BL cells use both promoter regions. Thus, the virus can use two alternative programs, depending on the cell phenotype. The "EBNA-1 only" program is activated from the Q-promoter. In cells with an immunoblastic (LCL or BL group III) phenotype, the upstream Cp/Wp promoters generate a 100 kb. long pre-mRNA, from which all the EBNAs are spliced. As a rule, only one of the two programs is used for each phenotype, except for the BL group III cells that began as group I but subsequently developed into a more LCL-like cell. Such cells used both promoter regions, with or without activation of the lytic cycle. SN - 0385-0684 UR - https://www.unboundmedicine.com/medline/citation/10895161/Cell_phenotype_dependent_splicing_reflecting_differential_promoter_usage_for_EBNA_transcripts_in_EBV_carrying_cells_ DB - PRIME DP - Unbound Medicine ER -