Transcripts originating in intron 1 of the HSD11 (11β-Hydroxysteroid dehydrogenase) gene encode a truncated polypeptide that is enzymatically inactive

Jihad Obeid, Kathleen M. Curnow, Javier Aisenberg, Perrin C. White

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

There is evidence for the presence in the kidney of more than one isoform of 11β-hydroxysteroid dehydrogenase (11HSD), an enzyme that interconverts cortisol and cortisone (in rodents, corticosterone and 11-dehydrocorticosterone). A specific isoform might arise from transcripts in the kidney that are known to originate in intron 1; translation from these transcripts is predicted to initiate at the codon that in the full-length rat enzyme encodes Met27. Alignment of the full-length rat and human 11HSD sequences with other members of the short chain dehydrogenase family suggests that initiation of translation at Met27 might yield a functional enzyme, since the amino-termini of most of these enzymes occur at equivalent positions. We confirmed that short transcripts are found in the kidney and are detectable at lower levels in the liver and lung. In vitro transcription and translation of short cDNA demonstrated that the AUG encoding Met27 is indeed a functional initiation codon. However, Chinese hamster ovary cells transfected with short cDNA in the pCMV4 vector expressed apparently low levels of the corresponding truncated polypeptide and had no 11HSD activity. Thus, the functional significance of transcripts originating in intron 1 is unclear.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalMolecular Endocrinology
Volume7
Issue number2
StatePublished - Feb 1993

Fingerprint

11-beta-Hydroxysteroid Dehydrogenases
Introns
Peptides
Enzymes
Kidney
Genes
Protein Isoforms
Complementary DNA
Initiator Codon
Cortisone
Corticosterone
Cricetulus
Codon
Hydrocortisone
Ovary
Rodentia
Oxidoreductases
Lung
Liver

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Transcripts originating in intron 1 of the HSD11 (11β-Hydroxysteroid dehydrogenase) gene encode a truncated polypeptide that is enzymatically inactive. / Obeid, Jihad; Curnow, Kathleen M.; Aisenberg, Javier; White, Perrin C.

In: Molecular Endocrinology, Vol. 7, No. 2, 02.1993, p. 154-160.

Research output: Contribution to journalArticle

@article{08a4c95585ba48e1bcc6dc8e641a051a,
title = "Transcripts originating in intron 1 of the HSD11 (11β-Hydroxysteroid dehydrogenase) gene encode a truncated polypeptide that is enzymatically inactive",
abstract = "There is evidence for the presence in the kidney of more than one isoform of 11β-hydroxysteroid dehydrogenase (11HSD), an enzyme that interconverts cortisol and cortisone (in rodents, corticosterone and 11-dehydrocorticosterone). A specific isoform might arise from transcripts in the kidney that are known to originate in intron 1; translation from these transcripts is predicted to initiate at the codon that in the full-length rat enzyme encodes Met27. Alignment of the full-length rat and human 11HSD sequences with other members of the short chain dehydrogenase family suggests that initiation of translation at Met27 might yield a functional enzyme, since the amino-termini of most of these enzymes occur at equivalent positions. We confirmed that short transcripts are found in the kidney and are detectable at lower levels in the liver and lung. In vitro transcription and translation of short cDNA demonstrated that the AUG encoding Met27 is indeed a functional initiation codon. However, Chinese hamster ovary cells transfected with short cDNA in the pCMV4 vector expressed apparently low levels of the corresponding truncated polypeptide and had no 11HSD activity. Thus, the functional significance of transcripts originating in intron 1 is unclear.",
author = "Jihad Obeid and Curnow, {Kathleen M.} and Javier Aisenberg and White, {Perrin C.}",
year = "1993",
month = "2",
language = "English (US)",
volume = "7",
pages = "154--160",
journal = "Molecular Endocrinology",
issn = "0888-8809",
publisher = "The Endocrine Society",
number = "2",

}

TY - JOUR

T1 - Transcripts originating in intron 1 of the HSD11 (11β-Hydroxysteroid dehydrogenase) gene encode a truncated polypeptide that is enzymatically inactive

AU - Obeid, Jihad

AU - Curnow, Kathleen M.

AU - Aisenberg, Javier

AU - White, Perrin C.

PY - 1993/2

Y1 - 1993/2

N2 - There is evidence for the presence in the kidney of more than one isoform of 11β-hydroxysteroid dehydrogenase (11HSD), an enzyme that interconverts cortisol and cortisone (in rodents, corticosterone and 11-dehydrocorticosterone). A specific isoform might arise from transcripts in the kidney that are known to originate in intron 1; translation from these transcripts is predicted to initiate at the codon that in the full-length rat enzyme encodes Met27. Alignment of the full-length rat and human 11HSD sequences with other members of the short chain dehydrogenase family suggests that initiation of translation at Met27 might yield a functional enzyme, since the amino-termini of most of these enzymes occur at equivalent positions. We confirmed that short transcripts are found in the kidney and are detectable at lower levels in the liver and lung. In vitro transcription and translation of short cDNA demonstrated that the AUG encoding Met27 is indeed a functional initiation codon. However, Chinese hamster ovary cells transfected with short cDNA in the pCMV4 vector expressed apparently low levels of the corresponding truncated polypeptide and had no 11HSD activity. Thus, the functional significance of transcripts originating in intron 1 is unclear.

AB - There is evidence for the presence in the kidney of more than one isoform of 11β-hydroxysteroid dehydrogenase (11HSD), an enzyme that interconverts cortisol and cortisone (in rodents, corticosterone and 11-dehydrocorticosterone). A specific isoform might arise from transcripts in the kidney that are known to originate in intron 1; translation from these transcripts is predicted to initiate at the codon that in the full-length rat enzyme encodes Met27. Alignment of the full-length rat and human 11HSD sequences with other members of the short chain dehydrogenase family suggests that initiation of translation at Met27 might yield a functional enzyme, since the amino-termini of most of these enzymes occur at equivalent positions. We confirmed that short transcripts are found in the kidney and are detectable at lower levels in the liver and lung. In vitro transcription and translation of short cDNA demonstrated that the AUG encoding Met27 is indeed a functional initiation codon. However, Chinese hamster ovary cells transfected with short cDNA in the pCMV4 vector expressed apparently low levels of the corresponding truncated polypeptide and had no 11HSD activity. Thus, the functional significance of transcripts originating in intron 1 is unclear.

UR - http://www.scopus.com/inward/record.url?scp=0027400590&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027400590&partnerID=8YFLogxK

M3 - Article

C2 - 8469231

AN - SCOPUS:0027400590

VL - 7

SP - 154

EP - 160

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 2

ER -