Alternative titles; symbols
HGNC Approved Gene Symbol: RBMY1A1
Cytogenetic location: Yq11.223 Genomic coordinates (GRCh38): Y:21,534,879-21,559,683 (from NCBI)
Ma et al. (1993) reported the isolation and characterization of a gene family located within interval 6 (subinterval XII-XIV) of Yq11.23, a region of approximately 200 kb that, when deleted, is associated with azoospermia or severe oligospermia (see 415000 for a discussion of this so-called 'azoospermia factor' (AZF) region). Analysis of the predicted protein products suggested a possible role in RNA processing or translational control during early spermatogenesis. The expression of the genes appeared to be testis-specific, and the genes showed a male-specific conservation of expression in DNA from several other mammals.
Delbridge et al. (1997) reviewed the literature on the RBM1 gene family. Expression of the human RBM1 gene family is confined to the spermatogonia and early primary spermatocytes in the lining of the seminiferous tubules in adults, but expression of the RBM1 gene family has also been demonstrated in the testis of 2-year-old and prepubertal boys, indicating that the RBM1 gene family may have an additional role in germ cell development. RBM1 is present as multiple copies in all eutherian species examined, including primates, rabbit, pig, cattle, sheep, and mouse. The RBM1 genes encode RNA-binding proteins containing a single N-terminal RNA-binding motif and a C-terminal auxiliary domain with 4 repeated segments with a high proportion of glycine, serine, and arginine residues, typical of many RNA-binding proteins. Two other genes that map to the same small region of the long arm of the human Y chromosome and are often deleted in azoospermic men are DAZ (400003) and TSPY (480100).
To investigate the number of functional RBM genes on the Y chromosome, Chai et al. (1997) studied RBM expression by use of RT-PCR of RBM transcripts and by characterizing numerous RBM cDNA clones. A total of 27 RT-PCR and 19 cDNA clones were sequenced. Whereas the RT-PCR clones pointed to the existence of at least 6 RBM subfamilies (RBM-I to RBM-VI), the cDNA clones indicated that only RBM-I is actively transcribed and encodes functional proteins. A total of 6 RBM-I genes were identified, which produced 4 polypeptides due to some silent base substitutions. Transcripts of each gene are alternatively spliced to generate protein isoforms with 3 or 4 SRGY boxes, thus greatly increasing the complexity of the products of the RBM gene family.
Ma et al. (1993) determined that the YRRM family, which includes RBMY1A1, comprises at least 15 copies clustered at chromosome Yq11.23, of which many are pseudogenes but at least 2 are transcribed.
Venables et al. (2000) used a yeast 2-hybrid system to show that RBM, the RBMX gene product hnRNPG, and a novel testis-specific relative hnRNPGT (RBMXL2; 605444) interact with Tra2-beta (602719), an activator of pre-mRNA splicing that is ubiquitous but highly expressed in testis. RBM and Tra2-beta colocalize in 2 major domains in human spermatocyte nuclei. Incubation with the protein interaction domain of RBM inhibited splicing in vitro of a specific pre-mRNA substrate containing an essential enhancer bound by Tra2-beta. The RNA-binding domain of RBM affected 5-prime splice site selection. The authors concluded that the hnRNPG family of proteins is involved in pre-mRNA splicing and hypothesized that RBM may be involved in Tra2-beta-dependent splicing in spermatocytes.
Ma et al. (1993) detected deletions of YRRM sequences in 2 oligospermic patients with no previously detected mutation.
Repping et al. (2004) identified the b2/b3 deletion within the AZFc region (see 415000) of the Y chromosome, in which all 6 copies of the RBMY gene are deleted. The b2/b3 deletion has no obvious effect on fitness.
Delbridge et al. (1997) demonstrated that RBM1, but not DAZ or TSPY, has a Y-linked homolog in marsupials that is transcribed in the testis. This suggests that RBM1 has been retained on the Y chromosome because of a critical male-specific function. Marsupial RBM1 is closely related to human RBM1, but lacks the amplification of an exon.
An active X-borne homolog of the Y-borne RBMY gene (RBMX; 300199) was demonstrated in humans and marsupials by Delbridge et al. (1999) and in the mouse by Mazeyrat et al. (1999). Delbridge et al. (1999) and Mazeyrat et al. (1999) found that the RBMX-like gene on chromosome 6p12, known only as a cDNA with 60% sequence similarity to RBMY, is a processed pseudogene of RBMX. Delbridge et al. (1999) suggested that RBMY and RBMX evolved from a gene on the mammalian proto-X and -Y pair at least 130 million years ago, before the divergence of eutherian and metatherian mammals.
By evolutionary analysis, Shi et al. (2019) showed that the RBMY1 gene family had some of the highest levels of variation in copy number and structural organization for any human gene. The high variability was a consequence of both high levels of increase and decrease in tandem clusters and additional gross rearrangements, including inversions.
Chai, N. N., Salido, E. C., Yen, P. H. Multiple functional copies of the RBM gene family, a spermatogenesis candidate on the human Y chromosome. Genomics 45: 355-361, 1997. [PubMed: 9344660] [Full Text: https://doi.org/10.1006/geno.1997.4944]
Delbridge, M. L., Harry, J. L., Toder, R., Waugh O'Neill, R. J., Ma, K., Chandley, A. C., Marshall Graves, J. A. A human candidate spermatogenesis gene, RBM1, is conserved and amplified on the marsupial Y chromosome. Nature Genet. 15: 131-136, 1997. Note: Erratum: Nature Genet. 15: 411 only, 1997. [PubMed: 9020837] [Full Text: https://doi.org/10.1038/ng0297-131]
Delbridge, M. L., Lingenfelter, P. A., Disteche, C. M., Marshall Graves, J. A. The candidate spermatogenesis gene RBMY has a homologue on the human X chromosome. (Letter) Nature Genet. 22: 223-224, 1999. [PubMed: 10391206] [Full Text: https://doi.org/10.1038/10279]
Ma, K., Inglis, J. D., Sharkey, A., Bickmore, W. A., Hill, R. E., Prosser, E. J., Speed, R. M., Thomson, E. J., Jobling, M., Taylor, K., Wolfe, J., Cooke, H. J., Hargreave, T. B., Chandley, A. C. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 75: 1287-1295, 1993. [PubMed: 8269511] [Full Text: https://doi.org/10.1016/0092-8674(93)90616-x]
Mazeyrat, S., Saut, N., Mattei, M.-G., Mitchell, M. J. RBMY evolved on the Y chromosome from a ubiquitously transcribed X-Y identical gene. (Letter) Nature Genet. 22: 224-226, 1999. [PubMed: 10391207] [Full Text: https://doi.org/10.1038/10282]
Repping, S., van Daalen, S. K. M., Korver, C. M., Brown, L. G., Marszalek, J. D., Gianotten, J., Oates, R. D., Silber, S., van der Veen, F., Page, D. C., Rozen, S. A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region. Genomics 83: 1046-1052, 2004. [PubMed: 15177557] [Full Text: https://doi.org/10.1016/j.ygeno.2003.12.018]
Shi, W., Louzada, S., Grigorova, M., Massaia, A., Arciero, E., Kibena, L., Ge, X. J., Chen, Y., Ayub, Q., Poolamets, O., Tyler-Smith, C., Punab, M., Laan, M., Yang, F., Hallast, P., Xue, Y. Evolutionary and functional analysis of RBMY1 gene and copy number variation on the human Y chromosome. Hum. Molec. Genet. 28: 2785-2798, 2019. [PubMed: 31108506] [Full Text: https://doi.org/10.1093/hmg/ddz101]
Venables, J. P., Elliott, D. J., Makarova, O. V., Makarov, E. M., Cooke, H.J., Eperon, I. C. RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2-beta and affect splicing. Hum. Molec. Genet. 9: 685-694, 2000. [PubMed: 10749975] [Full Text: https://doi.org/10.1093/hmg/9.5.685]