Browsing by Author "Park, Sunhee"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Heat-induced ribosome pausing triggers mRNA co-translational decay in Arabidopsis thaliana(Oxford University Press, 2015-04-06) Merret, R´emy; Nagarajan, Vinay K.; Carpentier, Marie-Christine; Park, Sunhee; Favory, Jean-Jacques; Descombin, Julie; Picart, Claire; Charng, Yee-yung; Green, Pamela J.; Deragon, Jean-Marc; Bousquet-Antonelli, C´ ecile; R´emy Merret, Vinay K. Nagarajan, Marie-Christine Carpentier, Sunhee Park, Jean-Jacques Favory, Julie Descombin, Claire Picart, Yee-yung Charng, Pamela J. Green, Jean-Marc Deragon and C´ ecile Bousquet-Antonelli; Nagarajan, Vinay K.; Park, Sunhee; Green, Pamela J.The reprogramming of gene expression in heat stress is a key determinant to organism survival. Gene expression is downregulated through translation initiation inhibition and release of free mRNPs that are rapidly degraded or stored. In mammals, heat also triggers 5′-ribosome pausing preferentially on transcripts coding for HSC/HSP70 chaperone targets, but the impact of such phenomenon on mRNA fate remains unknown. Here, we provide evidence that, in Arabidopsis thaliana, heat provokes 5′-ribosome pausing leading to the XRN4-mediated 5′-directed decay of translating mRNAs. We also show that hindering HSC/HSP70 activity at 20°C recapitulates heat effects by inducing ribosome pausing and co-translational mRNA turnover. Strikingly, co-translational decay targets encode proteins with high HSC/HSP70 binding scores and hydrophobic N-termini, two characteristics that were previously observed for transcripts most prone to pausing in animals. This work suggests for the first time that stress-induced variation of translation elongation rate is an evolutionarily conserved process leading to the polysomal degradation of thousands of ‘non-aberrant’ mRNAs.Item Heat-induced ribosome pausing triggers mRNA co-translational decay in Arabidopsis thaliana(Oxford University Press, 2015-04-06) Merret, R´emy; Nagarajan, Vinay K.; Carpentier, Marie-Christine; Park, Sunhee; Favory, Jean-Jacques; Descombin, Julie; Picart, Claire; Charng, Yee-yung; Green, Pamela J.; Deragon, Jean-Marc; Bousquet-Antonelli, C´ ecile; R´emy Merret, Vinay K. Nagarajan, Marie-Christine Carpentier, Sunhee Park, Jean-Jacques Favory, Julie Descombin, Claire Picart, Yee-yung Charng, Pamela J. Green, Jean-Marc Deragon and C´ ecile Bousquet-Antonelli; Nagarajan, Vinay K.; Park, Sunhee; Green, Pamela J.The reprogramming of gene expression in heat stress is a key determinant to organism survival. Gene expression is downregulated through translation initiation inhibition and release of free mRNPs that are rapidly degraded or stored. In mammals, heat also triggers 5 -ribosome pausing preferentially on transcripts coding for HSC/HSP70 chaperone targets, but the impact of such phenomenon on mRNA fate remains unknown. Here, we provide evidence that, in Arabidopsis thaliana, heat provokes 5 -ribosome pausing leading to the XRN4-mediated 5 -directed decay of translating mRNAs. We also show that hindering HSC/HSP70 activity at 20◦C recapitulates heat effects by inducing ribosome pausing and co-translational mRNA turnover. Strikingly, co-translational decay targets encode proteins with high HSC/HSP70 binding scores and hydrophobic N-termini, two characteristics that were previously observed for transcripts most prone to pausing in animals. This work suggests for the first time that stress-induced variation of translation elongation rate is an evolutionarily conserved process leading to the polysomal degradation of thousands of ‘nonaberrant’ mRNAs.Item Initial Observations of Cell-Mediated Drug Delivery to the Deep Lung(Cognizant Communication Corporation, 2011) Glaum, M.; Kumar, Arun (Professor); El-Badri, N.; Mohapatra, S.; Haller, E.; Park, Sunhee; Patrick, L.; Nattkemper, L.; Vo, D.; Cameron, D. F.; Kumar, A., Glaum, M., El-Badri, N., Mohapatra, S., Haller, E., Park, S., Patrick, L., Nattkemper, L., Vo, D., Cameron, D. F.; Kumar, Arun (Professor)Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route. Additionally, Sertoli cells were preloaded with chitosan nanoparticles coupled with the anti-inflammatory compound curcumin and then injected intravenously into control or experimental mice with deep lung inflammation. By 24 h postinjection, most of the curcumin load ( 90%) delivered in the injected Sertoli cells was present and distributed throughout the lungs, including the perialveloar sac area in the lower lungs. This was based on the high-density, positive quantification of both nanoparticles and curcumin in the lungs. There was a marked positive therapeutic effect achieved 24 h following curcumin treatment delivered by this Sertoli cell nanoparticle protocol (SNAP). Results identify a novel and efficient protocol for targeted delivery of drugs to the deep lung mediated by extratesticular Sertoli cells. Utilization of SNAP delivery may optimize drug therapy for conditions such as ARDS, status asthmaticus, pulmonary hypertension, lung cancer, and complications following lung transplantation where the use of high concentrations of anti-inflammatory drugs is desirable, but often limited by risks of systemic drug toxicity.