Disease relevance of stau

• In the course of a two-hybrid screen with the NS1 protein of influenza virus, a human clone capable of coding for a protein with high homology to the Staufen protein from Drosophila melanogaster (dmStaufen) was identified [1].
• These six residues are conserved in the two dsRBMs for which structural information is available (Escherichia coli RNase III and Drosophila melanogaster staufen) and in many other members of the dsRBM protein family [2].
• Yfia shows a global beta-alpha-beta-beta-beta-alpha folding topology similar to its homologue HI0257 of Haemophilus influenzae and the double-strand-binding domain of Drosophila Staufen protein [3].

High impact information on stau

• Staufen binds prospero RNA in its 3'UTR [4].
• Hence staufen also acts zygotically, downstream of inscuteable, to effect aspects of neuroblast asymmetry [4].
• Here we show that staufen protein colocalizes with bcd mRNA at the anterior, and that this localization depends upon its association with the mRNA [5].
• We report the cloning and sequencing of staufen and show that staufen protein is one of the first molecules to localize to the posterior pole of the oocyte, perhaps in association with oskar RNA [6].
• We show that genes known to interact directly with Hb are not responsible for its spatial precision, but that the maternal gene staufen may be crucial [7].

Biological context of stau

• Inscuteable and Staufen interact and colocalize with prospero RNA on the apical cortex of interphase neuroblasts [4].
• Inscuteable and Staufen mediate asymmetric localization and segregation of prospero RNA during Drosophila neuroblast cell divisions [4].
• The proposed mechanism includes Staufen (Stau), an RNA binding protein that appears essential to precision scaling (Nature 415 (2002) 798) [8].
• By inducing cytoplasmic streaming in wild-type oocytes during mid-oogenesis, we show that premature cytoplasmic streaming can displace staufen protein from the posterior pole, but not gurken mRNA from around the oocyte nucleus [9].
• In conclusion, we have shown that the mammalian homologues of Dm stau are expressed in germ cells in both male and female mice, consistent with a role for these RNA binding proteins in mammalian gametogenesis [10].

Anatomical context of stau

• We have shown previously that endogenous STAU associates specifically with injected bcd mRNA 3'-untranslated region (UTR), resulting in the formation of characteristic RNA-protein particles that are transported along microtubules of the mitotic spindles in a directed manner [11].
• miranda localizes staufen and prospero asymmetrically in mitotic neuroblasts and epithelial cells in early Drosophila embryogenesis [12].
• Inscuteable becomes uniform at the cortex, whereas Prospero and Staufen become cytoplasmic; inhibitor washout leads to recovery of microfilaments and asymmetric localization of all three proteins [13].
• Here we use in vitro culture of neuroblasts to investigate the role of intrinsic and extrinsic cues and the cytoskeleton in asymmetric localization of Inscuteable, Prospero and Staufen proteins [13].
• When Stau1 or Stau2 functions are compromised in embryos by injecting antisense morpholino modified oligonucleotides or dominant-negative Stau peptides, germ layer patterning is not affected [14].

Associations of stau with chemical compounds

• Staufen- and FMRP-Containing Neuronal RNPs Are Structurally and Functionally Related to Somatic P Bodies [15].
• We show that while the staufen-like protein does not co-purify with microtubules from ovaries using standard procedures it does so under conditions of motor-entrapment, specifically in the presence of AMP-PNP [16].
• A recombinant dsRNA binding domain from the Drosophila staufen protein and human protein kinase R were crosslinked by UV or methylene blue to a series of dsRNAs [17].
• In cell fractionation and sucrose gradient assays, Staufen co-fractionates with intact ribosomes and polysomes, but not with the isolated 40 S ribosomal subunit [18].

Physical interactions of stau

• Upon injection into the embryo, bcd transcripts specifically interact with staufen, and we have mapped the sequences required to three regions of the 3'UTR, each of which is predicted to form a long stem-loop [5].
• Thus, a complex containing oskar mRNA and Staufen may be transported along microtubules to the posterior pole by kinesin I [19].
• The RNA-binding protein Staufen from rat brain interacts with protein phosphatase-1 [20].

Regulatory relationships of stau

• Injection of the different bcd RNA variants into living Drosophila embryos shows that all elements that inhibit RNA dimerization in vitro prevent formation of localized particles containing Staufen [21].

Other interactions of stau

• In addition, we discuss the possible biological role of the Oskar-Staufen interaction [22].
• Furthermore, miranda function is required for the asymmetric localization of Staufen [23].
• We have explored interactions between these gene products at the molecular level and find that Oskar interacts directly with Vasa and Staufen, in a yeast two-hybrid assay [22].
• In the model, Stau is released from both ends of the embryo and relocalizes hb RNA by increasing its mobility [8].
• Staufen protein associates with the 3'UTR of bicoid mRNA to form particles that move in a microtubule-dependent manner [5].

Analytical, diagnostic and therapeutic context of stau

• CONCLUSIONS: Convergent findings from our behavioral screen for memory mutants and DNA microarray analysis of transcriptional responses during memory formation in normal animals suggest the involvement of the pumilio/staufen pathway in memory [24].
• Northern blot and in situ hybridization showed that staufen is expressed both maternally and zygotically [25].
• Furthermore, pull-down and immunoprecipitation experiments suggest a direct interaction between Staufen 1 and the ribosomal protein P0 in vitro as well as in cells [18].

References