Cell type-dependent gene regulation by Staufen2 in conjunction with Upf1

<p>Abstract</p> <p>Background</p> <p>Staufen2 (Stau2), a double-stranded RNA-binding protein, is a component of neuronal RNA granules, which are dendritic mRNA transport machines. Although Stau2 is thought to be involved in the dendritic targeting of several mRNAs in neurons, the mechanism whereby Stau2 regulates these mRNAs is unknown. To elucidate the functions of Stau2, we screened for novel binding partners by affinity purification of GST-tagged Stau2 from 293F cells.</p> <p>Results</p> <p>Three RNA helicases, RNA helicase A, Upf1 and Mov10, were identified in Stau2-containing complexes. We focused our studies on Upf1, a key player in nonsense-mediated mRNA decay. Stau2 was found to bind directly to Upf1 in an RNA-independent manner <it>in vitro</it>. Tethering Stau2 to the 3'-untranslated region (UTR) of a reporter gene had little effect on its expression in HeLa cells. In contrast, when the same tethering assay was performed in 293F cells, we observed an increase in reporter protein levels. This upregulation of protein expression by Stau2 turned out to be dependent on Upf1. Moreover, we found that in 293F cells, Stau2 upregulates the reporter mRNA level in an Upf1-independent manner.</p> <p>Conclusions</p> <p>These results indicate that the recruitment of Stau2 alone or in combination with Upf1 differentially affects the fate of mRNAs. Moreover, the results suggest that Stau2-mediated fate determination could be executed in a cell type-specific manner.</p

Exportin-5 orthologues are functionally divergent among species

Exportin-5, an evolutionarily conserved nuclear export factor belonging to the importin-β family of proteins, is known to play a role in the nuclear export of small noncoding RNAs such as precursors of microRNA, viral minihelix RNA and a subset of tRNAs in mammalian cells. In this study, we show that the exportin-5 orthologues from different species such as human, fruit fly and yeast exhibit diverged functions. We found that Msn5p, a yeast exportin-5 orthologue, binds double-stranded RNAs and that it prefers a shorter 22 nt, double-stranded RNA to ∼80 nt pre-miRNA, even though both of these RNAs share a similar terminal structure. Furthermore, we found that Drosophila exportin-5 binds pre-miRNAs and that amongst the exportin-5 orthologues tested, it shows the highest affinity for tRNAs. The knockdown of Drosophila exportin-5 in cultured cells decreased the amounts of tRNA as well as miRNA, whereas the knock down of human exportin-5 in cultured cells affected only miRNA but not tRNA levels. These results indicate that double-stranded RNA binding ability is an inherited functional characteristic of the exportin-5 orthologues and that Drosophila exportin-5 functions as an exporter of tRNAs as well as pre-miRNAs in the fruit fly that lacks the orthologous gene for exportin-t

Construction of Illuminance Distribution Measurement System and Evaluation of Illuminance Convergence in Intelligent Lighting System

Abstract-There have been various studies on illuminance evaluation in offices, but due to the difficulty of measurement by using many illuminance sensors, few examples of measurement of illuminance distribution in offices exist until present. We have proposed an Intelligent Lighting System which is not the existing lighting system providing uniform illuminance, but can provide different illuminance by a worker&apos;s work content and preference. Illuminance distribution evaluation is important for the Intelligent Lighting System since it provides different illuminances to each worker. In this study, we structured a system which visualizes the illuminance data obtained from more than 160 illuminance sensors as real-time illuminance distribution, and report the result of evaluating the dynamic change of illuminance in the Intelligent Lighting System. Furthermore, we mention the measurement result of illuminance distribution in an actual office where the Intelligent Lighting System was introduced

Fruit Quolity of'Gros Colman'Grapes Produced on Virus-free Vines

The Grape cultivar 'Gros Coleman'(Vitis vinifera)is the latest-maturing variety in japan,mainly cultivatde in green-houses in southern Okayama.Vines treated with virus-free treatments before raising in a nursery bed have been introduced in the last desade to improve the fuit quality,especially skin coloration and sugar content.However,some growers feel that the fruit taste from treated vines tends to deteriorate earlier than from untreated vines. We investigated change in the qualities of the berries produced on treated and untreated vines from October to January.After analysing skin color,berry turgidity,and juice constituents,we concluded that the palatability of berries on virus-free vines might be lessened in late December or thereafter of the rapid decrease in amino acids such as glutamic acid,glutamine,and alanine,which considerrably affects fruit taste.岡山県南部で施設栽培されている晩熟性ブドウの’グローコールマン’では、果実の品質を高めるためにウイルスフリー樹の導入が進められてきた。それによって、多くの場合は果実の着色や糖の蓄積が促進されるようになったが、樹によっては出荷最盛期の12月下旬になると果実の「張り」や食味が低下すると言われている。本研究で主産地の岡山市一宮地区内にある５ケ所の’グロー･コールマン’園で、ウイルスフリー樹と在来樹の果実の成熟を比較した結果、12月上旬から1月中旬までの間に果粒の「張り」や果汁の糖濃度が低下することは認められなかった。しかし、ウイルスフリー樹では果汁のアミノ酸が速く低下する傾向があり、それが食味の低下を引き起こす可能性があると推察される

Specialized Pro-Resolving Mediators Do Not Inhibit the Synthesis of Inflammatory Mediators Induced by Tumor Necrosis Factor-α in Synovial Fibroblasts

Background : Tumor necrosis factor (TNF)-α, a proinflammatory cytokine, is involved in the pathogenesis of rheumatoid arthritis (RA). The omega-3 unsaturated fatty acid-derived metabolites resolvin (Rv) D1, RvE1, and maresin-1 (MaR1) have been reported as anti-inflammatory lipid mediators and are known as specialized pro-resolving mediators (SPMs). In this study, we aimed to investigate the anti-inflammatory effects of SPMs on TNF-α-induced responses in synovial fibroblasts. Methods: We investigated the effects of SPMs on gene expression and/or production of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), interleukin (IL)-6, and matrix metalloproteinase (MMP)-3, which are involved in TNF-α-induced synovitis in RA or OA synovial fibroblasts, by quantitative real-time PCR. We also investigated the effects of SPMs on the mitogen-activated protein kinase (MAPK) signaling pathway by western blotting. Anti-inflammatory effects of SPMs were evaluated by applying SPMs to cultured synovial fibroblasts, followed by TNF-α stimulation. Results: The induction of COX-2, mPGES-1, IL-6, and MMP-3 by TNF-α in synovial fibroblasts was not suppressed by omega 3-derived SPMs regardless of their origin such as RA or OA. SPMs had no effect on lipid mediator receptor gene expression induce by TNF-α and did not inhibit the TNF-α-activated MAPK signaling pathway. The production of COX-2 and IL-6 protein was significantly decreased by p38 inhibitor. Conclusion: Despite reports on the anti-inflammatory effect of omega 3-derived SPMs, its anti-inflammatory effect on TNF-α-induced responses was not observed in synovial fibroblasts. The reason may be that SPMs have no suppressive effect on p38 activation, which plays an important role in the production of inflammatory cytokines in synovial fibroblasts

Multiple granulomatous lung lesions in a patient with Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus: a case report

INTRODUCTION: Granulomatous lesions are commonly encountered abnormalities in pulmonary pathology, and often pose a diagnostic challenge. We report an unusual case of granulomatous lung disease with uncommon characteristics, which developed following Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus. We aim to highlight a diagnostic approach for the condition and to raise awareness of the possibility of it being related to the immunological reaction caused by Epstein-Barr virus infection. CASE PRESENTATION: A 36-year-old Japanese man, who had been diagnosed with Epstein-Barr-virus-induced infectious mononucleosis, new-onset systemic lupus erythematosus, and secondary Sjögren’s syndrome three weeks previously, presented to our facility with fever and diffuse pulmonary infiltrates. A computed tomography scan of the chest revealed multiple small nodules in both lungs. Fiberoptic bronchoscopy with bronchoalveolar lavage revealed lymphocytosis with predominance of T lymphocytes. A histological examination of a lung biopsy taken during video-assisted thoracic surgery showed randomly distributed tiny granulomatous lesions with infiltration of eosinophils. The differential diagnoses included hypersensitivity pneumonitis, sarcoidosis, and pulmonary involvement of Crohn’s disease, systemic lupus erythematosus, and Sjögren’s syndrome, but the clinical and pathological findings were not consistent with any of these. Our patient’s condition did not improve; therefore, prednisolone therapy was started because of the possibility of specific immunological reactions associated with Epstein-Barr virus infection. After steroid treatment, our patient showed radiological and clinical improvement. CONCLUSIONS: To the best of our knowledge, this is the first case of a patient developing randomly distributed multiple granulomatous lung lesions with eosinophilic infiltrates after Epstein-Barr virus infection and systemic lupus erythematosus. On the basis of our data, we hypothesize that Epstein-Barr virus infection altered the immune response of our predisposed patient and contributed to the pathogenesis of the lung lesions. Our patient’s clinical response to steroid treatment was excellent