title: Expression of the two alternatively spliced PRKAR1A RNAs in human endocrine glands.
abstract: Heterozygous loss of function mutations in human PKAR1A gene (PRKAR1A) have been identified in patients with Carney complex (CNC), an autosomal dominant familial multiple neoplasia syndrome displaying different endocrine tumors, including adrenocortical tumors, GH-secreting pituitary tumors and thyroid adenomas. Although PRKAR1A is encoded by a single gene, it is transcribed from at least two different promoters, adjacent to different first non-coding exons (1a and 1b), giving rise to alternately spliced transcripts coding for identical proteins. The separate regulation of the two distinct promoters and the presence of multiple alternatively spliced first exons suggest a complex mechanism of PRKAR1A expression regulation. In order to investigate the relative expression of the two mRNA transcripts (1a and 1b) in human adult endocrine tissues involved in the determination of CNC phenotype, we selected 17 pituitary, 20 adrenal and seven thyroid tissues from tumoral and peri-tumoral lesion samples. Expression of the two transcripts was evaluated by semi-quantitative RT-PCR and real-time RT-PCR. This study first reports that human pituitary and thyroid tissues show a similar expression of the two transcripts, whereas in adrenal tissues transcript 1b is the most abundant one.
authors.affiliation: Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS, Padiglione Granelli, Via F. Sforza, 35, 20122 Milan, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Peverelli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantovani
authors.forename: Sara
authors.initials: S
authors.lastname: Bondioni
authors.forename: Caterina
authors.initials: C
authors.lastname: Pellegrini
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Lania
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Anna
authors.initials: A
authors.lastname: Spada
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017868:Cyclic AMP-Dependent Protein Kinases