title: DDX3X, the X homologue of AZFa gene DDX3Y, expresses a complex pattern of transcript variants only in the male germ line.
abstract: DDX3X, the functional X homologue of the major AZFa gene, DDX3Y, belongs to the highly conserved PL10-subfamily of DEAD-box RNA helicase genes which are functionally conserved from yeast to man. They are mainly involved in cell cycle control and translation initiation control of gene transcripts with long 5'UTR extensions containing complex secondary structures. Interestingly, in humans both gene copies were found to be expressed at different phases of human spermatogenesis. Whereas DDX3Y transcripts are translated only in premeiotic male germ cells, the DDX3X protein is expressed only in postmeiotic spermatids. In this study, we found that the major class of DDX3X transcripts in human testis become activated first after meiosis and at a specific core promoter not active in somatic tissues and not present upstream of the DDX3Y homologue. Two alternative 5'UTR transcript lengths are subsequently produced by an additional testis-specific 5'UTR splicing event. Both transcripts are mainly processed for polyadenylation in their proximal 3'UTR. A minor transcript class starting at the same male germ line-specific core promoter produces primary transcripts with an extremely long 3'UTR (∼ 17 kb), which is subsequently spliced at distinct sites resulting in six short 3'UTR splice variants (I-VI). Comparative analyses of the DDX3X transcripts in mouse and primates revealed that this complex pattern of male germ line-specific transcript variants first evolved in primates. Our data thus suggest complex translational control mechanism(s) for the human DDX3X gene locus functioning only in the male germ line and resulting in expression of its protein only in the postmeiotic spermatids.
authors.affiliation: Reproduction Genetics Unit, Department of Gynecological Endocrinology & Reproductive Medicine, University of Heidelberg, Heidelberg, Germany Present address: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Program of Functional Genomics and Cancer, CNRS UDS UMR 7104, INSERM U 964, 67404 Illkirch Cedex, France.
authors.forename: Marc-Alexander
authors.initials: MA
authors.lastname: Rauschendorf
authors.affiliation: Reproduction Genetics Unit, Department of Gynecological Endocrinology & Reproductive Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Zimmer
authors.affiliation: Reproduction Genetics Unit, Department of Gynecological Endocrinology & Reproductive Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ohnmacht
authors.affiliation: Reproduction Genetics Unit, Department of Gynecological Endocrinology & Reproductive Medicine, University of Heidelberg, Heidelberg, Germany peter.vogt@med.uni-heidelberg.de.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Vogt
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008540:Meiosis; D051379:Mice; D015778:Minor Histocompatibility Antigens; D026723:Polyadenylation; D011323:Primates; D013045:Species Specificity; D013087:Spermatids / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D015778:Minor Histocompatibility Antigens; C119332:DDX3X protein, human; C492034:DDX3Y protein, human; D053487:DEAD-box RNA Helicases
keywords: 5′UTR and 3′UTR transcript variants; DDX3X evolution; DDX3Y gene homologue; male germ line