Four 5‐Hydroxytryptamine7 (5‐HT7) Receptor Isoforms in Human and Rat Produced by Alternative Splicing: Species Differences Due to Altered Intron‐Exon Organization

• Published in: Journal of neurochemistry 1997-04, Vol.68 (4), p.1372-1381
• Main Authors: Heidmann, Doris E. A., Metcalf, Mark A., Kohen, Ruth, Hamblin, Mark W.
• Format: Article
• Language: English
• Subjects: Alternative splicing; Alternative Splicing - physiology; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Carboxyl terminus; Caudate Nucleus - chemistry; Chromosome Mapping; Cloning, Molecular; Exons - genetics; Fundamental and applied biological sciences. Psychology; G protein‐coupled receptor; Gene Expression - physiology; Hippocampus - chemistry; Humans; Introns - genetics; Isomerism; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; PCR; Protein Structure, Tertiary; Rats; Receptors, Serotonin - chemistry; Receptors, Serotonin - genetics; Reverse transcriptase; RNA, Messenger - analysis; RNA, Messenger - genetics; Sequence Analysis, DNA; Serotonin receptor; Species Specificity; Spleen - chemistry; Transcription. Transcription factor. Splicing. Rna processing
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1997.68041372.x

: The serotonin (5‐HT) 5‐HT7 receptor subtype is thought to mediate a number of physiological effects in mammalian brain and periphery. Previous studies suggested that alternative splicing might contribute to 5‐HT7 receptor diversity as well. We now report that alternative splicing in human and rat tissues produces four 5‐HT7 receptor isoforms that differ in their predicted C‐terminal intracellular tails. Human and rat partial 5‐HT7 cDNAs and intronic sequences were identified and compared. In rat tissues, three 5‐HT7 isoforms, here called 5‐HT7(a), 5‐HT7(b), and 5‐HT7(c), are found. Rat 5‐HT7(a) [448‐amino acid (aa)] and 5‐HT7(b) (435‐aa) forms arise from alternative splice donor sites. A third new isoform found in rat, 5‐HT7(c) (470‐aa), results from a retained exon cassette. Three 5‐HT7 mRNA isoforms were also identified in human tissues, where only one isoform was previously described. Two human isoforms represent 5‐HT7(a) and 5‐HT7(b) forms (445‐ and 432‐aa), but the third form does not correspond to 5‐HT7(c). Instead, it constitutes a distinct isoform, 5‐HT7(d) (479‐aa), resulting from retention of a separate exon cassette. 5‐HT7(d) transcripts are not present in rat because the 5‐HT7(d)‐specifying exon is absent from the rat 5‐HT7 gene. A frame‐shifting homologue of the rat 5‐HT7(c)‐specifying exon is present in the human gene but is not used in the human tissues examined. Tissue‐specific splicing differences are present in human between brain and spleen. These studies suggest that alternative splicing may contribute to diversity of 5‐HT7 receptor action and that the human and rat repertoires of 5‐HT7 splice variants are substantially different.