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Medientyp:
E-Artikel
Titel:
Isolation and Characterization of the Human Parathyroid Hormone-Like Peptide Gene
Beteiligte:
Mangin, Marguerite;
Ikeda, Kyoji;
Dreyer, Barbara E.;
Broadus, Arthur E.
Erschienen:
National Academy of Sciences of the United States of America, 1989
Erschienen in:
Proceedings of the National Academy of Sciences of the United States of America, 86 (1989) 7, Seite 2408-2412
Sprache:
Englisch
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
<p>A parathyroid hormone-like peptide (PTHLP) has recently been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The peptide appears to be encoded by a single-copy gene that gives rise to multiple mRNAs that are heterogeneous at both their 5<sup>′</sup> and their 3<sup>′</sup> ends. Alternative RNA splicing is responsible for the 3<sup>′</sup> heterogenelty and results in mRNAs encoding three different peptides, each with a unique C terminus. We have isolated and characterized the human PTHLP gene. The gene is a complex transcriptional unit spanning more than 12 kilobases of DNA and containing six exons. Two 5<sup>′</sup> exons encode distinct 5<sup>′</sup> untranslated regions and are separated by a putative promoter element, indicating that the gene either has two promoters or is alternatively spliced from a single promoter upstream of the first exon. The middle portion of the PTHLP gene, comprising exons 2-4, has an organizational pattern of introns and exons identical to that of the parathyroid hormone gene, consistent with a common ancestral origin of these two genes. Exon 4 of the PTHLP gene encodes the region common to all three peptides and the C terminus of the shortest peptide, and exons 5 and 6 encode the unique C termini of the other two peptides. Northern analysis of mRNAs from four human tumors of different histological types reveals the preferential use of 3<sup>′</sup> splicing patterns by individual tumors.</p>