Structure and expression of the variant melanin-concentrating hormone genes: only PMCHL1 is transcribed in the developing human brain and encodes a putative protein.
PMCHL1 and PMCHL2 are two copies of the so-called variant melanin-concentrating hormone (MCH) gene that are located, respectively, on human chromosome 5p14 and 5q13 and that emerged recently during primate evolution. They correspond to a 5'-end truncated version of the MCH gene mapped on chromosome 12q23 and encoding a neuropeptide precursor. The gene organization and regulation of the expression of the variant MCH genes in the human brain are the central issues we investigated. First, the structure and fine chromosomal mapping of the 5p and 5q variant MCH genes were established. These revealed several point mutations and length variations of one CA/TA repeat which allow discrimination between each copy. Using a combination of RACE-PCR, RT-PCR, and sequencing analysis, we provided strong evidence for the expression of the PMCHL1 gene but not the PMCHL2 gene in the human fetal, newborn, and adult brains. Sense, potentially coding, RNAs, as well as noncoding antisense RNAs, were identified and displayed a region-specific expression in the human brain. Strikingly, sense unspliced RNAs of the PMCHL1 gene carried a novel open reading frame and may produce an NLS-containing protein of 8 kDa named VMCH-p8. These transcripts were translated in vitro and in transfected COS cells. Therefore, the PMCHL1 gene provides a unique example of the generation of a gene in the Hominoidae lineage which is specifically transcribed in the developing human brain and has the capacity to be translated into a putative novel protein.
Viale
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Institut de Pharmacologie Moléculaire et Cellullaire, UPR 411 Centre National de la Recherche Scientifique, Valbonne, France.
Courseaux
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Presse
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Ortola
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Breton
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Jordan
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Nahon
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JL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D016466:CHO Cells; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D020451:Contig Mapping; D006224:Cricetinae; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D006822:Hybrid Cells; D007028:Hypothalamic Hormones / Q000235:genetics*; D008543:Melanins / Q000235:genetics*; D008969:Molecular Sequence Data; D010907:Pituitary Hormones / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; D020033:Protein Isoforms; D012313:RNA; C019463:melanin-concentrating hormone; D004247:DNA