Analysis of the gene and multiple messenger ribonucleic acids (mRNAs) encoding human gastrin-releasing peptide

alternate RNA splicing occurs in neural and endocrine tissue.

Eliot Spindel, M. D. Zilberberg, W. W. Chin

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Gastrin-releasing peptide (GRP), the mammalian homolog of the amphibian peptide bombesin, is encoded in man by a single gene located on chromosome 18. Restriction enzyme and DNA sequence analyses establish that the gene is 10 kilobases in size with two introns of 4.8 and 3.9 kilobases. Exon 1 encodes the 5'-untranslated region, the signal peptide, and the first 23 amino acids of GRP. Exon 2 encodes the remaining three complete amino acids of GRP and the first 74 amino acids of the GRP carboxy-terminal extension peptide. Hence, intron 1 interrupts the coding region of the bioactive portion of GRP between the first and second nucleotides for Gly, the 24th amino acid of GRP. Exon 3 encodes the remainder of the GRP-extension peptide and the 3'-untranslated region. Two GC-rich, potential regulatory sequences and a sequence associated with regulation by cAMP lie between the CAAT and TATA boxes; the primary transcriptional start site is located 30 bases downstream from the TATA box. The second intron has an alternate donor site at its 5'-end and an alternate acceptor site at its 3'-end. S1 nuclease mapping demonstrates that differential RNA splicing using these sites results in the similar expression of three GRP mRNAs in GRP-containing neurons (in stomach and brain) as well as in GRP-containing neuroendocrine cells (fetal lung). In addition, the pattern of RNA splicing is similar between normal tissue and neoplastic tissue (small cell carcinoma of the lung and medullary carcinoma of the thyroid).

Original languageEnglish (US)
Pages (from-to)224-232
Number of pages9
JournalMolecular endocrinology (Baltimore, Md.)
Volume1
Issue number3
StatePublished - Mar 1987
Externally publishedYes

Fingerprint

Gastrin-Releasing Peptide
RNA Splicing
Alternative Splicing
RNA
Genes
Introns
Amino Acids
Exons
TATA Box
Peptides
Chromosomes, Human, Pair 18
Bombesin
Neuroendocrine Cells
5' Untranslated Regions
Small Cell Lung Carcinoma
3' Untranslated Regions
Amphibians
Protein Sorting Signals
DNA Sequence Analysis
Stomach

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Analysis of the gene and multiple messenger ribonucleic acids (mRNAs) encoding human gastrin-releasing peptide: alternate RNA splicing occurs in neural and endocrine tissue.",
abstract = "Gastrin-releasing peptide (GRP), the mammalian homolog of the amphibian peptide bombesin, is encoded in man by a single gene located on chromosome 18. Restriction enzyme and DNA sequence analyses establish that the gene is 10 kilobases in size with two introns of 4.8 and 3.9 kilobases. Exon 1 encodes the 5'-untranslated region, the signal peptide, and the first 23 amino acids of GRP. Exon 2 encodes the remaining three complete amino acids of GRP and the first 74 amino acids of the GRP carboxy-terminal extension peptide. Hence, intron 1 interrupts the coding region of the bioactive portion of GRP between the first and second nucleotides for Gly, the 24th amino acid of GRP. Exon 3 encodes the remainder of the GRP-extension peptide and the 3'-untranslated region. Two GC-rich, potential regulatory sequences and a sequence associated with regulation by cAMP lie between the CAAT and TATA boxes; the primary transcriptional start site is located 30 bases downstream from the TATA box. The second intron has an alternate donor site at its 5'-end and an alternate acceptor site at its 3'-end. S1 nuclease mapping demonstrates that differential RNA splicing using these sites results in the similar expression of three GRP mRNAs in GRP-containing neurons (in stomach and brain) as well as in GRP-containing neuroendocrine cells (fetal lung). In addition, the pattern of RNA splicing is similar between normal tissue and neoplastic tissue (small cell carcinoma of the lung and medullary carcinoma of the thyroid).",
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T1 - Analysis of the gene and multiple messenger ribonucleic acids (mRNAs) encoding human gastrin-releasing peptide

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AU - Chin, W. W.

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N2 - Gastrin-releasing peptide (GRP), the mammalian homolog of the amphibian peptide bombesin, is encoded in man by a single gene located on chromosome 18. Restriction enzyme and DNA sequence analyses establish that the gene is 10 kilobases in size with two introns of 4.8 and 3.9 kilobases. Exon 1 encodes the 5'-untranslated region, the signal peptide, and the first 23 amino acids of GRP. Exon 2 encodes the remaining three complete amino acids of GRP and the first 74 amino acids of the GRP carboxy-terminal extension peptide. Hence, intron 1 interrupts the coding region of the bioactive portion of GRP between the first and second nucleotides for Gly, the 24th amino acid of GRP. Exon 3 encodes the remainder of the GRP-extension peptide and the 3'-untranslated region. Two GC-rich, potential regulatory sequences and a sequence associated with regulation by cAMP lie between the CAAT and TATA boxes; the primary transcriptional start site is located 30 bases downstream from the TATA box. The second intron has an alternate donor site at its 5'-end and an alternate acceptor site at its 3'-end. S1 nuclease mapping demonstrates that differential RNA splicing using these sites results in the similar expression of three GRP mRNAs in GRP-containing neurons (in stomach and brain) as well as in GRP-containing neuroendocrine cells (fetal lung). In addition, the pattern of RNA splicing is similar between normal tissue and neoplastic tissue (small cell carcinoma of the lung and medullary carcinoma of the thyroid).

AB - Gastrin-releasing peptide (GRP), the mammalian homolog of the amphibian peptide bombesin, is encoded in man by a single gene located on chromosome 18. Restriction enzyme and DNA sequence analyses establish that the gene is 10 kilobases in size with two introns of 4.8 and 3.9 kilobases. Exon 1 encodes the 5'-untranslated region, the signal peptide, and the first 23 amino acids of GRP. Exon 2 encodes the remaining three complete amino acids of GRP and the first 74 amino acids of the GRP carboxy-terminal extension peptide. Hence, intron 1 interrupts the coding region of the bioactive portion of GRP between the first and second nucleotides for Gly, the 24th amino acid of GRP. Exon 3 encodes the remainder of the GRP-extension peptide and the 3'-untranslated region. Two GC-rich, potential regulatory sequences and a sequence associated with regulation by cAMP lie between the CAAT and TATA boxes; the primary transcriptional start site is located 30 bases downstream from the TATA box. The second intron has an alternate donor site at its 5'-end and an alternate acceptor site at its 3'-end. S1 nuclease mapping demonstrates that differential RNA splicing using these sites results in the similar expression of three GRP mRNAs in GRP-containing neurons (in stomach and brain) as well as in GRP-containing neuroendocrine cells (fetal lung). In addition, the pattern of RNA splicing is similar between normal tissue and neoplastic tissue (small cell carcinoma of the lung and medullary carcinoma of the thyroid).

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