Variants of the 5′-untranslated sequence of human growth hormone receptor mRNA

Pekhletsky, Roman I.; Chernov, B. K.; Rubtsov, P. M.

doi:10.1016/0303-7207(92)90107-h

Cited by 79 publications

(46 citation statements)

References 21 publications

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“…One of these 5 UTR sequences is predominant in extrahepatic tissues (Adams 1995, Domene et al 1995, Lucy et al 1998, Moffat et al 1999a). This 5 UTR -designated L2 in the mouse (Southard et al 1995), 1B in ruminants (Adams 1995, Heap et al 1996, V2 in human (Pekhletsky et al 1992) and GHR 2 /V1 in the rat (Baumbach & Bingham 1995, Domene et al 1995) -has a highly conserved GC-rich sequence. The pattern of expression in mouse tissues shows that the associated promoter is responsible for the general expression of the mouse GHR/BP gene (Moffat et al 1999a, Yu et al 1999, and this is probably also the case in other species.…”

Section: Introductionmentioning

confidence: 99%

“…The pattern of expression in mouse tissues shows that the associated promoter is responsible for the general expression of the mouse GHR/BP gene (Moffat et al 1999a, Yu et al 1999, and this is probably also the case in other species. The other 5 UTR, which is liverspecific, is designated L1 in the mouse (Southard et al 1995), 1A in ruminants (O'Mahoney et al 1994, Heap et al 1995, V1 in the human and the baboon (Godowski et al 1989, Pekhletsky et al 1992 and GHR 1 /V2 in the rat (Baumbach et al 1989, Domene et al 1995. The relative level of expression of this 5 UTR has been assessed in mouse (Ilkbahar et al 1999, Moffat et al 1999a, rat (Baumbach & Bingham 1995), bovine (Lucy et al 1998) and ovine (Li et al 1999) liver.…”

Section: Introductionmentioning

confidence: 99%

“…Seven other 5 UTRs, V3-V9, have been reported for human GHR/BP cDNA (Godowski et al 1989, Pekhletsky et al 1992. In the rat, alternative 5 UTRs (V3-V5) that have no homology with the human 5 UTRs have been cloned (Frick & Goodman 1992, Domene et al 1995.…”

Section: Introductionmentioning

confidence: 99%

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Alternative 5'-untranslated regions of mouse GH receptor/binding protein messenger RNA are derived from sequences adjacent to the major L2 promoter

Moffat

Dao²,

Talamantes³

2000

Journal of Endocrinology

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Heterogeneity of 5 untranslated region (5 UTR) sequences is a common feature of growth hormone receptor/ binding protein (GHR/BP) mRNA from a number of species. Two major 5 UTR sequences (designated L1 and L2 in the mouse) have been cloned from rodents, ruminants and primates, and are known to correspond to transcripts generated from independently regulated promoters. A variable number of other 5 UTRs with diverse sequences have been cloned from rat, human and bovine tissues. To characterize alternative 5 UTR usage in mouse GHR/BP mRNA, we carried out 5 rapid amplification of cDNA ends using RNA from non-pregnant mouse liver and adipose tissue. Three novel 5 UTR sequences were obtained. Sequencing of genomic DNA revealed that exons corresponding to these three sequences are clustered within 1 kb downstream of the exon encoding 5 UTR L2, and the associated L2 promoter. The novel 5 UTRs are present at very low levels relative to the total pool of GHR/BP mRNA in liver, fat, kidney, and mammary gland as determined by ribonuclease protection assays. On the basis of these data, we propose that these 5 UTR sequences may result from the use of cryptic transcription start sites and splice donor sites under the influence of the adjacent L2 promoter/enhancer region.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alternative 5'-untranslated regions of mouse GH receptor/binding protein messenger RNA are derived from sequences adjacent to the major L2 promoter

Moffat

Dao²,

Talamantes³

2000

Journal of Endocrinology

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“…The diversity of the 5 untranslated region (5 UTR) of GHR mRNA in the human (Pekhletsky et al 1992, Zogopoulos et al 1997, ovine (O'Mahoney et al 1994, Adams 1995, bovine (Heap et al 1995) and rodent (Baumbach & Bingham 1995, Menon et al 1995 has suggested that, in all species, multiple promoter regions may regulate transcription of the GHR gene. In the human, eight different 5 UTR variants, numbered V1 to V8 according to their relative abundance, have been cloned from adult liver by 5 rapid amplification of cDNA ends (5 RACE) (Pekhletsky et al 1992).…”

Section: Introductionmentioning

confidence: 99%

“…In the human, eight different 5 UTR variants, numbered V1 to V8 according to their relative abundance, have been cloned from adult liver by 5 rapid amplification of cDNA ends (5 RACE) (Pekhletsky et al 1992). All eight variants have distinct nucleotide sequences and only converge at 11 nucleotides prior to the start site of translation in exon 2.…”

Section: Introductionmentioning

confidence: 99%

The baboon: a model for the study of primate growth hormone receptor gene expression during development

Zogopoulos

Nathanielsz

Hendy

et al. 1999

Journal of Molecular Endocrinology

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In subprimates, significant onset of growth hormone receptor (GHR) expression occurs only after birth whereas, in the human, GHR mRNA and protein are widely manifest from the first trimester of fetal life. Thus, it is likely that subprimates are not the best models for studying regulation of human GHR gene transcription, especially during early stages in development. Here we have explored the potential of the baboon as a more appropriate model. Baboon GHR cDNAs were cloned from postnatal liver by reverse transcription (RT)-PCR, using human GHRspecific primers. The encoded baboon GHR precursor protein has an identical signal peptide sequence to that of human and rhesus monkey GHRs, and the mature baboon GHR is also 620 amino acids long, with 95% and 98·5% amino acid identity to the human and rhesus monkey receptors respectively. Previous studies in the human have identified eight 5 untranslated region (5 UTR) variants of the GHR mRNA (V1 to V8, numbered according to their relative abundance). We cloned the baboon V1, V3 and V4 homologues by RT-PCR: these variants have a high degree (>92%) of sequence identity with their human counterparts and also diverge at an identical point, 12 nucleotides upstream of the start of translation. The expression pattern of these three GHR mRNA isoforms in baboon liver during development was characterized. Strong expression of baboon V1 and V4 was evident by 49 days of postnatal life (n=5, 49 days and adult (18·6-19·6 kg)); very low levels of V1, but not V4, were observed in younger animals (n=2, 6 and 30 days). In contrast, V3 5 UTR variant mRNA was present in all fetal (n=4, 141-155 days gestation) and postnatal (n=7, 6-19·6 days and adult (18·6 kg)) hepatic specimens examined. Analysis of postnatal kidney and lung (n=2, 19 and 19·6 kg) revealed that V3 transcripts are present in these tissues, but not V1 and V4. Together, these data demonstrate that, as in the human, baboon V1 and V4 expression is developmentally regulated and tissue specific, while the V3 isoform is more widely expressed. Therefore, it is likely that the regulatory regions of the baboon and human GHR genes are well conserved. Our findings suggest that the baboon is an appropriate animal model in which to define the mechanisms regulating GHR gene transcription during primate development.

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The Growth Hormone Receptor

Waters

1999

Comprehensive Physiology

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Variants of the 5′-untranslated sequence of human growth hormone receptor mRNA

Cited by 79 publications

References 21 publications

Alternative 5'-untranslated regions of mouse GH receptor/binding protein messenger RNA are derived from sequences adjacent to the major L2 promoter

Alternative 5'-untranslated regions of mouse GH receptor/binding protein messenger RNA are derived from sequences adjacent to the major L2 promoter

The baboon: a model for the study of primate growth hormone receptor gene expression during development

The Growth Hormone Receptor

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