Characterization of Proopiomelanocortin Transcripts in Human Nonpituitary Tissues

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 20; pp. 7261 - 7265
• Main Authors: Lacaze-Masmonteil, Thierry, De Keyzer, Yves, Luton, Jean-Pierre, Kahn, Axel, Bertagna, Xavier
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.10.1987; National Acad Sciences
• Subjects: Adrenal Glands - metabolism; Base Sequence; Biological and medical sciences; DNA probes; Exons; Fundamental and applied biological sciences. Psychology; Gels; Gene expression; Genes; Humans; Male; Messenger RNA; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Molecules; Organ Specificity; Pro-Opiomelanocortin - biosynthesis; Pro-Opiomelanocortin - genetics; Promoter regions; Promoter Regions, Genetic; RNA; RNA probes; RNA, Messenger - biosynthesis; Testes; Testis - metabolism; Thymus Gland - metabolism; Transcription, Genetic; Characterization; Human; Regulation(control); Messenger RNA; Proopiocortin; Tissue specificity; Gene expression; Mechanism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.20.7261

Proopiomelanocortin (POMC), the precursor to adrenocorticotropic hormone and other related peptides, was originally identified in the corticotropic cell. Recent evidence shows that POMC products are also normally present in a variety of nonpituitary tissues. To investigate this phenomenon in humans we looked for the presence and characteristics of POMC transcripts in various adult tissues. Blot hybridization analysis of normal adrenal, thymus, and testis RNAs revealed a small RNA species approximately 400 nucleotides shorter than the 1200-nucleotide pituitary species. Primer extension and S1 nuclease mapping studies showed that this small RNA lacked exon 1 and exon 2 of the gene, and it corresponded to a set of at least six molecules starting 41 to 162 nucleotides downstream from the 5′ end of exon 3. These RNAs appear to result from heterogeneous transcription initiation sites presumably under the control of ``GC box'' promoter sequences located in the 3′ end of intron 2. They cannot encode a complete POMC molecule, and the only truncated POMC molecules that could be translated would lack a signal peptide necessary for membrane translocation and precursor processing. The use of highly sensitive S1 nuclease mapping techniques with uniformly labeled single-stranded DNA probes allowed the detection of a small but definite amount of the ``normal,'' 1200-nucleotide, mRNA species. It is suggested that it is this POMC mRNA that is responsible for the local production of all the POMC peptides.