Disease relevance of Rbp9

• The female sterility phenotype of the Rbp9 mutants resulted from defects in oogenesis; the lack of Rbp9 activity caused the germarium region of the mutants to be filled with undifferentiated cystocytes [1].
• The Drosophila protein, Rbp9, is homologous to human Hu, which is reported to be involved in small cell lung cancer [2].

High impact information on Rbp9

• Female-sterile mutations at the dec-1 (defective chorion-1) locus of Drosophila severely disrupt the organization of the eggshell late in oogenesis [3].
• Female sterile (1) yolkless: a recessive female sterile mutation in Drosophila melanogaster with depressed numbers of coated pits and coated vesicles within the developing oocytes [4].
• In hypomorphic Rbp9 mutants, cystocytes differentiated into egg chambers; however, oocyte determination and positioning were perturbed [1].
• Requirement of RBP9, a Drosophila Hu homolog, for regulation of cystocyte differentiation and oocyte determination during oogenesis [1].
• These results suggest that RBP9 protein binds to bam mRNA to down regulate BAM protein expression, which is essential for the initiation of cystocyte differentiation into functional egg chambers [1].

Biological context of Rbp9

• Rbp9 is an RNA binding protein expressed mainly in the central nervous system of adult Drosophilamelanogaster [5].
• We then employed a Selex system to identify a consensus Rbp9 binding site (UUUXUUUU) [5].
• Taken together with the in vitro RNA binding results, the genetic evidence obtained strongly supports the hypothesis that Rbp9 functions as a regulator of RNA stability [5].
• Down regulation of extramacrochaetae mRNA by a Drosophila neural RNA binding protein Rbp9 which is homologous to human Hu proteins [5].
• Staining of the Rbp9 over-expressing transgenic ovaries with mitosis markers revealed almost no mitotic divisions in the transgenic germaria [6].

Anatomical context of Rbp9

• To test whether Rbp9 is also required for germline sex determination, we examined the sex transformation process of female germ cells in Rbp9 mutant flies [7].
• To examine the role of Rbp9, we over-expressed it ectopically in germline stem cells and early stage cystocytes that had not yet formed 16 cell clusters [6].
• Despite the predominant expression of RBP9 in nerve cells, mutational analysis revealed a female sterility phenotype rather than neuronal defects for Rbp9 mutants [1].
• Polytene chromosomes of good cytological quality from pseudonurse cells (PNCs) of fs(2)B and otu11 mutants were obtained, photomaps for otu11 mutants were constructed and the general characteristics of polytene chromosomes from salivary glands (SGs) and PNCs were compared [8].

Physical interactions of Rbp9

• Using in vitro RNA binding assays, we found that Rbp9 binds strongly to poly U sequences [5].

Regulatory relationships of Rbp9

• RBP9 appears to stimulate cystocyte differentiation by regulating the expression of bag-of-marbles (bam) mRNA, which encodes a developmental regulator of germ cells [1].

Other interactions of Rbp9

• UV crosslinking experiments demonstrated that Rbp9 interactsspecifically with emc mRNA [5].
• The detection of Sxl male transcripts and other male germline markers in Rbp9 mutant ovaries revealed that the Rbp9 mutation caused a partial germline sex transformation [7].
• Mutation of Rbp9 caused over-proliferation of cystocytes and generated an ovarian tumor phenotype [6].
• Upregulation seems to result from activation of the NF-kappaB pathway since we detected nuclear localization of Relish in Rbp9 mutant ovaries but not in wild type ovaries [2].
• The Drosophila RNA-binding protein, Staufen is required for germ cell formation, and mutations in stau result in a maternal effect grandchild-less phenotype (Schupbach,T., Weischaus, E., 1989. Female sterile mutations on the second chromosome of Drosophila melanogaster:1. Maternal effect mutations. Genetics 121, 101-17) [9].

References