title: Structure of the 5' region of the human hexokinase type I (HKI) gene and identification of an additional testis-specific HKI mRNA.
abstract: We previously reported the structure of the human hexokinase type I (HKI) gene and provided direct evidence of an alternative red blood cell-specific exon 1 located in the 5' flanking region of the gene. Three unique HKI mRNA species have also been described in human spermatogenic cells. These mRNAs contain a testis-specific sequence not present in somatic cell HKI, but lack the sequence for the porin-binding domain necessary for HKI to bind to porin on the outer mitochondrial membrane. The present study reports a new mRNA isoform, hHKI-td, isolated from human sperm. hHKI-td mRNA contains both a testis-specific sequence at the 5' end common to the three other mRNA isoforms and an additional unique sequence. Screening of a cosmid library and analysis of the cosmids containing the HKI gene revealed that testis-specific sequences are encoded by six different exons. Five of these exons are located upstream from the somatic exon 1 (5.6-30 kb) and one within intron 1. This study shows that a single human HKI gene spanning at least 100 kb encodes multiple transcripts that are generated by alternative splicing of different 5' exons. Testis-specific transcripts are probably produced by a separate promoter that induces the expression of the HKI gene in spermatogenic cells.
authors.affiliation: 'G. Fornaini' Institute of Biological Chemistry, University of Urbino, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Andreoni
authors.forename: A
authors.initials: A
authors.lastname: Ruzzo
authors.forename: M
authors.initials: M
authors.lastname: Magnani
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D006593:Hexokinase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000201:enzymology*
chemical_list: D018076:DNA, Complementary; D007527:Isoenzymes; D012333:RNA, Messenger; D006593:Hexokinase