Localization of a regulatory region on the 5′‐untranslated region of human hepatoma HepG2 γ‐glutamyltransferase mRNA and response to dexamethasone and antisense oligonucleotide treatment

Diederich, Marc; Wellman, Maria; Siest, Gérard

doi:10.1016/0014-5793(94)01293-8

Cited by 6 publications

(4 citation statements)

References 32 publications

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“…Common sequences termed exon IIa, IIb and IIc are not separated by introns, but they contain intron-donor and intron-acceptor sites at their boundaries. It has been shown that the HepG2 GGT mRNA 5 H UTR enhances the translation of the lucifearase mRNA in several transiently transfected cell lines [30] and that it contains glucocorticoid-responsive translational enhancers, within a stem and loop structure [31]. This regulatory element is localized, at the mRNA level, between bases 262 and 367 [31].…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that the HepG2 GGT mRNA 5 H UTR enhances the translation of the lucifearase mRNA in several transiently transfected cell lines [30] and that it contains glucocorticoid-responsive translational enhancers, within a stem and loop structure [31]. This regulatory element is localized, at the mRNA level, between bases 262 and 367 [31]. At the genomic level, this structure comprises the 26 most distal 3 H bases of exon IIc, all the bases of exon IIb and the first 60 bases of exon IIa.…”

Section: Discussionmentioning

confidence: 99%

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Structure of the 5' sequences of the human gamma-glutamyltransferase gene

Visvikis¹,

Pawlak²,

Accaoui³

et al. 2001

Eur J Biochem

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In humans, five distinct mRNAs code for g-glutamyltransferase (GGT). Their coding regions are identical and their 5 H untranslated regions exhibit both common and typespecific sequences. To elucidate the mecanisms that generate these different mRNAs, we cloned and determined the structure of the 5 H region of the human GGT gene. The common regions of the 5 H UTR are encoded by five exons, localized within a 2.4-kb region of the genomic DNA. Three of them are separated only by intron-donor or intronacceptor sites at their boundaries. Alternative splicing of these exons may determine the unique pattern of the different GGT mRNA 5 H UTRs in a tissue-specific manner.In addition, we have isolated a genomic fragment containing the most distal 5 H sequences of the major GGT mRNA in HepG2 cells. Primer extension analysis revealed one major transcription initiation site while 5 H RACE indicated that one more distal initiation site could be present. In the putative promoter sequence neither classical TATA or CAAT boxes were found. However, sites for AP1, AP2, CREB, GRE and SP1 transcription factors were identified. Chimeric plasmids, containing this genomic region fused to the luciferase gene, were transiently expressed in three cell lines of different origin: HeLa cells, ovarian carcinoma A2780 cells and V79 lung fibroblasts. The significant promoter activities obtained indicate a transcription start within this region. However, differences in the level of expression were found between the different cell lines used. These data suggest that the human GGT gene employs regulatory sequences and alternative splicing, and gene expression may therefore be regulated in tissue specific and cell-type-specific manners.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Structure of the 5' sequences of the human gamma-glutamyltransferase gene

Visvikis¹,

Pawlak²,

Accaoui³

et al. 2001

Eur J Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…Common sequences termed exon IIa, IIb and IIc are not separated by introns, but they contain intron‐donor and intron‐acceptor sites at their boundaries. It has been shown that the HepG2 GGT mRNA 5′ UTR enhances the translation of the lucifearase mRNA in several transiently transfected cell lines [30] and that it contains glucocorticoid‐responsive translational enhancers, within a stem and loop structure [31]. This regulatory element is localized, at the mRNA level, between bases 262 and 367 [31].…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that the HepG2 GGT mRNA 5′ UTR enhances the translation of the lucifearase mRNA in several transiently transfected cell lines [30] and that it contains glucocorticoid‐responsive translational enhancers, within a stem and loop structure [31]. This regulatory element is localized, at the mRNA level, between bases 262 and 367 [31]. At the genomic level, this structure comprises the 26 most distal 3′ bases of exon IIc, all the bases of exon IIb and the first 60 bases of exon IIa.…”

Section: Discussionmentioning

confidence: 99%

Structure of the 5′ sequences of the human γ‐glutamyltransferase gene

Visvikis

Pawlak

Accaoui

et al. 2001

European Journal of Biochemistry

Self Cite

View full text Add to dashboard Cite

In humans, five distinct mRNAs code for gamma-glutamyltransferase (GGT). Their coding regions are identical and their 5' untranslated regions exhibit both common and type-specific sequences. To elucidate the mecanisms that generate these different mRNAs, we cloned and determined the structure of the 5' region of the human GGT gene. The common regions of the 5' UTR are encoded by five exons, localized within a 2.4-kb region of the genomic DNA. Three of them are separated only by intron-donor or intron-acceptor sites at their boundaries. Alternative splicing of these exons may determine the unique pattern of the different GGT mRNA 5' UTRs in a tissue-specific manner. In addition, we have isolated a genomic fragment containing the most distal 5' sequences of the major GGT mRNA in HepG2 cells. Primer extension analysis revealed one major transcription initiation site while 5' RACE indicated that one more distal initiation site could be present. In the putative promoter sequence neither classical TATA or CAAT boxes were found. However, sites for AP1, AP2, CREB, GRE and SP1 transcription factors were identified. Chimeric plasmids, containing this genomic region fused to the luciferase gene, were transiently expressed in three cell lines of different origin: HeLa cells, ovarian carcinoma A2780 cells and V79 lung fibroblasts. The significant promoter activities obtained indicate a transcription start within this region. However, differences in the level of expression were found between the different cell lines used. These data suggest that the human GGT gene employs regulatory sequences and alternative splicing, and gene expression may therefore be regulated in tissue specific and cell-type-specific manners.

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