Activating transcription factor (ATF) 5 is a transcription factor belonging to the ATF/cAMP-response element-binding protein gene family. We previously reported that ATF5 mRNA expression increased in ...response to amino acid limitation. The ATF5 gene allows transcription of mRNAs with at least two alternative 5′-untranslated regions (5′-UTRs), 5′-UTRα and 5′-UTRβ, derived from exon1α and exon1β. 5′-UTRα contains highly conserved sequences, in which the upstream open reading frames (uORFs) uORF1 and uORF2 are found in many species. This study was designed to investigate the potential role of 5′-UTRs in translational control. These 5′-UTRs differentially determined translation efficiency from mRNA. The presence of 5′-UTRα or 5′-UTRβ represses translation from the downstream ATF5 ORF. Moreover, 5′-UTRα-regulated translational repression is released by amino acid limitation or NaAsO2 exposure. This release was not seen for 5′-UTRβ. Mutation of uAUG2 in the uORF2 of 5′-UTRα restored the basal expression and abolished the positive regulation by amino acid limitation or arsenite exposure. We demonstrated that phosphorylation of eukaryotic initiation factor 2α was required for amino acid limitation-induced translational regulation of ATF5. Furthermore, arsenite exposure activated the exogenously expressed heme-regulated inhibitor kinase and induced the phosphorylation of eukaryotic initiation factor 2α in nonerythroid cells. These results suggest that translation of ATF5 is regulated by the alternative 5′-UTR region of its mRNA, and ATF5 may play a role in protecting cells from amino acid limitation or arsenite-induced oxidative stress.
We previously reported that activating transcription factor 5 (ATF5) mRNA increases in response to amino acid limitation, and that this increase is dependent on mRNA stabilization. The ATF5 gene ...allows transcription of mRNAs with two alternative 5′‐UTRs, 5′‐UTRα and 5′‐UTRβ, derived from exon 1α and exon 1β. 5′‐UTRα contains the upstream open reading frames uORF1 and uORF2. Phosphorylation of eukaryotic initiation factor 2α during the integrated stress response had been previously shown to lead to bypassing of uORF2 translation and production of ATF5 protein. Translation of uORF2 is expected to result in translational termination at a position 125 nucleotides upstream of the exon junction, and this fits the criterion of a nonsense‐mediated decay target mRNA. We investigated the potential role of 5′‐UTRα in the control of mRNA stabilization, and found that 5′‐UTRα reduced the stability of ATF5 mRNA. 5′‐UTRα‐regulated destabilization of mRNA was suppressed by knockdown of the nonsense‐mediated decay factors Upf1 and Upf2. Mutation of the downstream AUG (uAUG2) rendered mRNA refractory to Upf1 and Upf2 knockdown. Moreover, 5′‐UTRα‐regulated down‐regulation was hindered by amino acid limitation and tunicamycin treatment, and stress‐induced phosphorylation of eukaryotic initiation factor 2α was involved in stabilization of ATF5 mRNA. These studies show that ATF5 mRNA is a naturally occurring normal mRNA target of nonsense‐mediated decay, and provide evidence for linkage between stress‐regulated translational regulation and the mRNA decay pathway. This linkage constitutes a mechanism that regulates expression of stress response genes.
Activating transcription factor 5 (ATF5) mRNA increases in response to environmental stress and this increase is dependent on mRNA stabilization. We show that ATF5 mRNA is a naturally‐occurring normal mRNA target of NMD, and provide evidence of linkage between stress‐regulated translational regulation and the mRNA decay pathway, which constitutes a mechanism regulating expression of stress response genes.
This study develops an analysis method for estimating the process of corrosion in concrete, including initial corrosion and the onset of corrosion-induced cracking. The method is suitable for ...application in rationalizing the verification of the durability of salt-damaged RC structures. Corrosion deterioration is computed by coupling the analysis of structure with the analysis of reinforcement corrosion. A method of calculating macro-cell corrosion in consideration of macro-cell corrosion current density is also proposed, focusing on cathodic elements of a reinforcing bar. The proposed analytical method is validated against dry-wet cyclic tests with salt solution to simulate macro-cell corrosion. We verify the accuracy of the method by confirming the non-uniformity of the concrete before cracking and, by coupling the analysis with structural analysis, investigating how the expansion ratio of corrosion products and diffusion coefficient of chloride ions affect the onset of corrosion, the time of initial corrosion cracking, the chloride ion density and the corrosion amount. This paper is based on an original paper (Suzuki et al. 2014) written in Japanese.
Recently wood is being promoted as a primary material used for public structures. With this promotion, the use of double-skinneDSiding (DS) is being incorporated in new buildings, and as older wooden ...structures are now being reinforced and reformed for continued use, DS is being incorporated in these buildings as well. We examined the efficacy of DS for maintaining a comfortable thermal environment within buildings. We used accumulated temperature data taken from our experiment location, a public school classroom environment, in the Tokyo Metropolitan area to better understand the use of DS for maintaining a comfortable temperature environment within the building. For our research, we focused on the following two topics: (1) Analysis of the data collected over a year at the experimental site1 We used an existing wooden structure that had had DS added to it. We were able to note the change in the room temperature with the addition of DS. In the summer, the inside of the DS with natural ventilation had a rate of circulation of 2027 m3/h, and with the fan, the amount of air circulation was noted as 13.1 times per hour. With DS, direct sunshine was reduced by 47.2% and helped to reduce energy consumption for cooling by 20%, and the PMV±0.5 was within the comfort zone. In the winter, sunlight warmed the DS, and the warmed air was pulled into the room via the floor ventilation, and when the temperature of the DS room was compared with a room without DS, the room with DS had a temperature 5° higher. The interior wall and floor surface temperature also rose by the vents installed in three areas in the room. The temperature of the inner glass surface of the DS was stable throughout the day contributing to the comfort of the room. During the nighttime, the fan could be stopped, and the use of the warmed air accumulated in the daytime was used to maintain warmth in the room. During the intermediate seasons, the use of the fan to circulate the air from the natural ventilation in the DS and the floor ventilation system was incorporated. With natural ventilation of the DS, the removal of the heat of about 30W/m2 occurred, and the DS room had a 5° differentiation in temperature when compared with a room without DS. (2) Examination of the Simulation Model for various environmental and climatic conditions The LESCOM-mint program was used to simulate the amount of energy required to maintain a heating and air system when DS is used for a wooden structure. Actual temperature data accumulated as well as theoretical considerations were combined to gain an understanding of the air and heating neeDS according to different climatic environments. We examined actual temperature measurements and the theoretical value for the summer and found both measurements to be in agreement. When considering the application of these findings for an elementary school environment, we determined that for optimal energy saving and maintenance of a comfortable environment a regular classroom should be on the southern side of the building and open space on the northern side, with DS of 1.4m placed on the southern wall. Through the use of the latest data collected from the Japanese Meteorological Agency (SDP) for Tokyo between 2010 and 2015, and the data collected from Sapporo and Naha from 2015, we have found that in areas like Tokyo, the adoption of DS is an energy-saving way to maintain a comfortable environment. In Sapporo, the warming effects and reduction in energy usage is also quite effective. For Naha, DS is effective in hot and humid environments.
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