Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm

Abstract

The association of abnormal spermatogenesis in men with Y chromosome deletions suggests that genes important for spermatogenesis have been removed from these individuals. Recently, genes encoding two putative RNAbinding proteins (RBM and DAZ͞SPGY) have been mapped to two different regions of the human Y chromosome. Both of these genes encode proteins that contain a single RNA recognition motif and a (different) internally repeating sequence. Y-linked RBM homologues are found in all mammalian species. We have raised an antiserum to RBM and used it to show that RBM is a nuclear protein expressed in fetal, prepubertal, and adult male germ cells. The distribution of RBM protein in the adult correlates with the pattern of transcriptional activity in spermatogenesis, suggesting that RBM is involved in the nuclear metabolism of newly synthesized RNA. RBM sequences are found on both arms of the Y chromosome making genotype-phenotype correlations difficult for this gene family. To address the location of the functional genes and the consequences of their deletion, we examined a panel of men with Y chromosome deletions and known testicular pathologies using this antiserum. This approach enabled us to map a region of the Y chromosome essential for RBM expression. In the absence of detectable RBM expression we see stages of germ cell development up to early meiosis, but not past this point into the haploid phase of spermatogenesis.

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…Deletions of the AZFb region include at least one functional copy of the RBMY1 gene. A family of PRY genes, essential in the regulation of apoptosis is also found in the AZFb region [53]. Whereas small AZFb deletions have been related to variable testicular phenotypes [54], larger AZFb deletions and those that include genes PRY1/PRY2 seem to cause complete meiotic arrest [34].…”

Human male infertility and its genetic causes

“…Thus, in 1995, it was demonstrated that DAZ mutations (Yq11.23) cause various forms of human male infertility that range from oligospermia to azoospermia 4, 5. In 1997, it was reported that RBMY (Yq11.223) mutations cause azoospermia via meiotic arrest5, 6 and, in 1999, it was shown that USP9Y (Yq11.2) mutations lead to azoospermia that is secondary to hypospermatogenesis 5, 7. The azoospermia factor (AZF) region on the Y chromosome is one of the most intensively studied regions in male infertility 8, 9.…”

A single nucleotide polymorphism in SPATA17 may be a genetic risk factor for Japanese patients with meiotic arrest

“…Genetic causes of azoospermia include chromosomal abnormalities, Y-chromosome microdeletions and several specific gene mutations/deletions affecting genes, such as DAZ, RBMY, USP9Y and SYCP3 [1][2][3][4][5]. As Y-chromosome deletions account for only 16.0% of men with infertility [6], azoospermia in many infertile men may be caused by autosomal gene mutations.…”