Complex transcriptional control of the AZFa gene DDX3Y in human testis

Abstract

The human DEAD-box Y (DBY) RNA helicase (aka DDX3Y) gene is thought to be the major azoospermia factor a (AZFa) gene in proximal Yq11. Men with its deletion display no somatic pathologies, but suffer from complete absence of germ cells. Accordingly, DDX3Y protein is expressed only in the germline in spermatogonia, although the transcripts were found in many tissues. Here, we show the complex transcriptional control of a testis-specific DDX3Y transcript class with initiation at different sites upstream of the gene’s open reading frame (5′Untranslated Region; UTR) and with polyadenylation in their proximal 3′UTR. The most distal transcriptional start site (TSS; ∼1 kb upstream) was mapped in MSY2, a Y-specific minisatellite. As this testis-specific 5′UTR was subsequently processed by three alternative splicing events, it has been tentatively designated ‘exon-T’(estis). The MSY2 sequence unit was also found upstream of the mouse Ddx3y gene. However, only after its tandem amplification on the Y chromosome of Platyrrhini (new world monkeys) and Catarrhini (old world monkeys) did MSY2 become part of a novel distal promoter for DDX3Y expression in testis tissue and provides a second transcriptional start site (T-TSS-II) in Catarrhini. We therefore suggest that the development of a novel distal DDX3Y promoter in primates, which is activated only in testis tissue, is probably part of the gene’s germline translation control.

Genome-wide comprehensive analysis of human helicases

“…49 In a recent study it has been reported that the human DBY RNA helicase gene is the major azoospermia factor a (AZFa) gene. 50 Men with its deletion display no somatic pathologies, but suffer from complete absence of germ cells. 50 Accordingly, DDX3Y protein is expressed only …”

“…50 Men with its deletion display no somatic pathologies, but suffer from complete absence of germ cells. 50 Accordingly, DDX3Y protein is expressed only …”

Progress in understanding the molecular functions of DDX3Y (DBY) in male germ cell development and maintenance

“…Both proteins are expressed in the testes; however, DDX3Y is found predominantly at premeiotic stages in spermatogonial cells, whereas DDX3X is detected later in spermatids (15,16,20). This divergent expression pattern arises due to complex transcriptional and translational control mechanisms (21,22) and it seems to predetermine presumed specific functions of DDX3Y in premeiotic spermatogenesis steps. Testis-specific DDX3Y transcription initiates from a distal promoter that takes place within upstream Y-specific minisatellite MSY2 repeats (21).…”

“…Testis-specific DDX3Y transcription initiates from a distal promoter that takes place within upstream Y-specific minisatellite MSY2 repeats (21). This distal promoter region for DDX3Y on the Y chromosome appears to be conserved in primates; however, it is not active upstream of the mouse Ddx3y genе (21). It has been shown that mouse homologue Ddx3y is expressed widely in all analyzed tissues (23).…”

“…This divergent expression pattern arises due to complex transcriptional and translational control mechanisms (21,22) and it seems to predetermine presumed specific functions of DDX3Y in premeiotic spermatogenesis steps. Testis-specific DDX3Y transcription initiates from a distal promoter that takes place within upstream Y-specific minisatellite MSY2 repeats (21). This distal promoter region for DDX3Y on the Y chromosome appears to be conserved in primates; however, it is not active upstream of the mouse Ddx3y genе (21).…”