Organization and Evolution of the Human Growth Hormone Receptor Gene 5'-Flanking Region

Goodyer, Cindy Gates

doi:10.1210/en.142.5.1923

Cited by 24 publications

(41 citation statements)

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“…The strong gut expression pattern is also consistent with a role in the processing of dietary components. However, alignment of the NAALADL2 protein sequence with other members of the M28B metallopeptidase family reveals that it often does not possess favoured amino acids at certain key positions that are highly conserved and that are envisaged to be critically important for metallopeptidase function (because of a role in the active site or in metal binding; for sequence alignments, see Goodyer et al 2001 ; Merops database, http://merops.sanger.co.uk/). Although significantly related to N-acetylated alphalinked acidic dipeptidase, the NAALADL2 protein is likely to have developed a somewhat different function.…”

Section: Discussionmentioning

confidence: 99%

“…growth hormone receptor, neuropeptide YY 5 receptor ( Goodyer et al 2001 ;Parker and Xia 1999 ). Alternative 5′ UTR splicing in such systems has often been viewed as regulating gene expression but evolutionary conservation of the 5′UTR exons of NAALADL2 appears to be limited, as has often been found in interspecies comparative analyses ( Nurtdinov et al 2003 ).…”

Section: Discussionmentioning

confidence: 99%

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A giant novel gene undergoing extensive alternative splicing is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3

et al. 2004

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Cornelia de Lange syndrome (CdLS) is a rare developmental malformation syndrome characterised by mental handicap, growth retardation, distinctive facial features and limb reduction defects. The vast majority of CdLS cases are sporadic. We carried out a high density bacterial artificial chromosome (BAC) microarray comparative genome hybridisation screen but no evidence was found for a consistent pattern of microdeletion/micro-duplication. As an alternative, we focused on identifying chromosomal regions spanning associated translocation breakpoints. We prioritised the distal 3q region because of the occurrence, in a classical CdLS patient, of a de novo balanced translocation with a breakpoint at 3q26.3 and of reports of phenotypic overlap between cases of mild CdLS and individuals trisomic for the 3q26-q27 region. We show that the 3q26.3 breakpoint severs a previously uncharacterised giant gene, NAALADL2, containing at least 32 exons spanning 1.37 Mb. Northern blot analysis identified up to six different transcripts in the 1-10 kb range with strongest expression in kidney and placenta; embryonic expression was largely confined to duodenal and stomach endoderm, mesonephros, metanephros and pancreas. Transcript analysis identified extensive alternative splicing leading to multiple 5′ and 3′ untranslated regions and variable coding sequences. Multiple protein isoforms were defined by different N-terminal regions (with at least four alternative initiating methionine codons), and by differential protein truncation/use of alternative C-terminal sequences attributable to alternative splicing/polyadenylation. Outside the N-terminal regions, the predicted proteins showed significant homology to N-acetylated alpha-linked acidic dipeptidase and transferrin receptors. Mutation screening of NAALADL2 in a panel of CdLS patient DNA samples failed to identify patient-specific mutations. We discuss the possibility that the 3q26.3 translocation could nevertheless contribute to pathogenesis. Tonkin et al.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A giant novel gene undergoing extensive alternative splicing is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3

et al. 2004

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“…Only one of them contained the iron-responsive element and exhibited regulation of translation activity depending on iron concentration. Developmental and tissue-specific regulation of expression of the human growth hormone receptor was shown to correlate with alternative use of 5ЈUTR exons (39). Thus, the different 5ЈUTR splice forms of RAG1 mRNA may regulate both tissue specific expression and the amounts of protein produced.…”

Section: Cd3mentioning

confidence: 99%

Extrathymic TCR Gene Rearrangement in Human Small Intestine: Identification of New Splice Forms of Recombination Activating Gene-1 mRNA with Selective Tissue Expression

Bas

Hammarström

2003

The Journal of Immunology

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Two new 5′-untranslated region (5′UTR) exons were identified in the human gene for the lymphocyte-specific endonuclease recombination activating gene-1 (RAG1) required for the somatic recombination yielding functional Ag receptors. These 5′UTR exons were used in three different splice forms by jejunal lymphocytes of the T cell lineage. RAG1 mRNA containing the previously described 5′UTR exon was not expressed in these cells. Conversely, one of the new 5′UTR exons was not expressed in thymus. The new RAG1 mRNA splice forms were all expressed in immature T cells (CD2+CD7+CD3−). This cell population also expressed high levels of mRNA for the pre-T α-chain. In situ hybridization demonstrated jejunal cells expressing the new splice forms of RAG1 mRNA, both intraepithelially and in lamina propria. Pre-T α-chain mRNA-expressing cells were detected at the same sites. These results strongly suggest ongoing TCR gene rearrangement in human small intestinal mucosa, yielding T cells specially adapted for this environment. This seems to be achieved by two parallel processes, extrathymic T cell development and peripheral Ag-driven TCR editing.

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“…Nine variants of GH-R mRNAs were identified in humans and in cattle (V1-V9 and 1 A-II, respectively) (Goodyer et al, 2001;Jiang and Lucy, 2001a). In the cattle, variant 1A is exclusively expressed in the liver and transcriptionally controlled by the liver-specific transcription factor hepatocyte -nuclear factor-4 (HNF-4) (Jiang and Lucy, 2001b).…”

Section: Introductionmentioning

confidence: 99%

“…In the cattle, variant 1A is exclusively expressed in the liver and transcriptionally controlled by the liver-specific transcription factor hepatocyte -nuclear factor-4 (HNF-4) (Jiang and Lucy, 2001b). Moreover, it has been suggested that expression of different transcripts is under developmental-and tissue-dependent regulation (Goodyer et al, 2001;Menon et al, 2001). Despite a growing amount of information concerning the isoforms of GH-R mRNA, so far no data are available on 5'-UTR heterogeneity in relation to the functional activity of GH-R.…”

Section: Introductionmentioning

confidence: 99%

Ligand-binding activity of growth hormone receptor (GH-R) in bulls of different breeds with identified GH-R genotypes

Grochowska¹,

Gajewska²,

Snochowski³

et al. 2002

J. Anim. Feed Sci.

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The relationship between the ligand-binding activity of growth hormone receptor (GH-R) and polymorphism \nAlul, Accl and Stul sites in the 5' flanking region of bovine GH-R gene was examined. The study was performed on twenty six 15-month old bulls of dairy (Friesians) and beef breeds (Charolais, Limousine, Piemontese, Aberdeen Angus, Hereford). Receptor binding capacity (B max ) and dissociation constant (K d ) for GH-R were determined by the Scatchard method. The polymorphism in the GH-R gene was analyzed by PCR-RFLP technique. Our results showed significant differences in the liver GH-R B and K. between the dairy and beef breeds. B was greater (P<0.05)in Polish Friesians as compared to the beef breeds, while K d revealed the lowest figure in the dairy breed (P<0.01). No significant differences were found in the B max and K d values between genotypes within the 5' flanking region of bovine GH-R gene. In conclusion, ligand-binding activity of the liver GH receptors was shown to differ between the dairy and beef bulls. Furthermore, the polymorphism in the 5' regions of GH-R gene seems to have no influence on ligand-binding properties of the liver GH receptor in cattle.

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Organization and Evolution of the Human Growth Hormone Receptor Gene 5'-Flanking Region

Cited by 24 publications

References 0 publications

A giant novel gene undergoing extensive alternative splicing is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3

A giant novel gene undergoing extensive alternative splicing is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3

Extrathymic TCR Gene Rearrangement in Human Small Intestine: Identification of New Splice Forms of Recombination Activating Gene-1 mRNA with Selective Tissue Expression

Ligand-binding activity of growth hormone receptor (GH-R) in bulls of different breeds with identified GH-R genotypes

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