Disease relevance of RBMY2KP

• In conclusion, to date, the USP9Y gene has been considered as one of the major Y-linked spermatogenesis genes, based on both its position within the AZFa region and previous reports that correlated USP9Y mutation to severe spermatogenic failure and infertility [1].
• Gastroprotective peptide trefoil factor family 2 gene is activated by upstream stimulating factor but not by c-Myc in gastrointestinal cancer cells [2].
• Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae [3].
• Interactions between the double-stranded RNA binding motif and RNA: definition of the binding site for the interferon-induced protein kinase DAI (PKR) on adenovirus VA RNA [4].
• The Y-linked ribosomal protein S4, Mat-8, and EST AA307912 were highly expressed in benign prostatic hyperplasia tissue [5].

Psychiatry related information on RBMY2KP

• The activity of the Y-linked Sry gene during a critical period of gonadal differentiation is the normal trigger for testis determination and subsequent male development in mammals [6].

High impact information on RBMY2KP

• Although candidate genes have been identified in all three regions, no case of spermatogenic failure has been traced to a point mutation in a Y-linked gene, or to a deletion of a single Y-linked gene [7].
• This hypothesis has been supported by the observation that, among primates, Y-linked genes evolved more rapidly than homologous X-linked genes [8].
• Low variability in a Y-linked plant gene and its implications for Y-chromosome evolution [9].
• ZFX evidently escaped X inactivation in proto-eutherians, which also possessed a very similar Y-linked gene; both characteristics were retained in most extant orders, but not in myomorph rodents [10].
• These Y-linked genes may form part of a coregulated group of genes which function during spermatogenesis [11].

Biological context of RBMY2KP

• Genetic evidence that a Y-linked gene in man is homologous to a gene on the X chromosome [12].
• RNA-binding motif (RBM) genes are found on all mammalian Y chromosomes and are implicated in spermatogenesis [13].
• We have mapped the protein domains responsible for mediating these interactions and expressed the mouse RBM interaction region as a bacterial fusion protein [13].
• Although Parp-2(-/-) spermatocytes exhibit normal telomere dynamics and normal chromosome synapsis, they display defective meiotic sex chromosome inactivation associated with derailed regulation of histone acetylation and methylation and up-regulated X- and Y-linked gene expression [14].
• This model was originally inferred from the occurrence of few Y-linked genetic traits, pairing of the X and Y chromosomes during male meiosis and, more recently, the existence of X-Y homologous genes [15].

Anatomical context of RBMY2KP

• Within human germ cells, RBM protein shows a similar nuclear distribution to components of the pre-mRNA splicing machinery [13].
• Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities [16].
• This tissue-restricted expression is in marked contrast with the wider distribution of all the other Family 2 cystatins, since cystatin C is expressed in all these tissues and the secretory gland cystatins are present in saliva, seminal plasma, and tears [17].
• RBM expression was detectable in spermatogonia, spermatocytes, and round spermatids in biopsies of men with obstructive azoospermia and normal spermatogenesis [18].
• The design of the current study is unique in its assessment of the state of germ cell differentiation in dysgenetic gonads by the use of the RBM protein, which was expressed only in normal germ cells but not in those of CIS [19].

Associations of RBMY2KP with chemical compounds

• The cystatin D sequence contains all regions of relevance for cysteine proteinase inhibitory activity and also the 4 cysteine residues that form disulfide bridges in the other members of cystatin Family 2 [17].
• A mutant form of the family 2 PspA with a deletion within the choline-binding region was also produced [3].
• We have cloned and characterized two genomic loci encoding the human type II gonadotropin-releasing hormone (GnRH) receptor and RNA-binding motif protein-8 (RBM8A) [20].
• From studies in the NTERA pluripotential cell line (which differentiates along neuronal and spermatogenic pathways in response to retinoic acid), it emerges that the X and Y-linked genes are regulated differently [21].

Analytical, diagnostic and therapeutic context of RBMY2KP

• Microarray analysis of seminiferous tubules isolated from XX/Sry testes confirmed the missing expression of several Y-linked genes and the alterations in the expression profile of genes associated with spermiogenesis [22].
• Comparative DNA analysis indicates that TGIFLX originated from retrotransposition of TGIF2, located on 20q11.2-12, onto the X Chromosome. RT-PCR analysis reveals that both X- and Y-linked genes are specifically expressed in adult testis [23].
• High-resolution fluorescence in situ hybridization of human Y-linked genes on released chromatin [24].
• The most successful method used for the isolation of Y-linked genes included the screening of a male complementary DNA (cDNA) library with the probe obtained by degenerate oligonucleotide-primed polymerase chain reaction (PCR) of the microdissected Y chromosomes [25].

References