記述言語：英語   掲載種別：研究論文（学術雑誌）  

Translation regulation is crucial for cellular homeostasis. Recent studies have demonstrated that, in addition to the conventional AUG start codon, eukaryotic mRNA can also possess non-canonical start codons. These non-canonical start codons, including non-AUG codons, can be found both upstream and downstream of the conventional AUG start codon. Translation of these non-canonical open reading frames (ORFs) has been implicated in the development of diseases, such as cardiac diseases, neurodegeneration and cancer development. Non-AUG translation initiation is regulated by eukaryotic initiation factor (eIF) 2A and eIF2D; however, their target non-canonical ORFs, roles in disease development, and the underlying precise mechanisms of translation regulation remain poorly understood. To address these gaps, we generated mice lacking either or both of Eif2a and Eif2d genes on an ICR background and investigated their cardiac function using echocardiography. The results indicated that simultaneous disruption of both Eif2a and Eif2d led to perinatal cardiac impairment, as evidenced by a significant reduction in cardiac contractility as measured by ejection fraction. Furthermore, the absence of phenotypic changes in single knockouts of either Eif2a or Eif2d suggests that eIF2A and eIF2D function redundantly in their molecular roles. These findings underscore the importance of non-AUG translation initiation in maintaining cardiac function and suggest its broader implications in other physiological and pathological processes. We propose the Eif2a and Eif2d double-knockout mice as a novel stress-sensitive animal model to investigate the molecular mechanisms of translation regulation and their contribution to disease pathogenesis.

DOI： 10.1538/expanim.25-0021

PubMed

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2024.150448

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A variety of bacteria, including Escherichia coli, are known to enter the viable but non-culturable (VBNC) state under various stress conditions. During this state, cells lose colony-forming activities on conventional agar plates while retaining signs of viability. Diverse environmental stresses including starvation induce the VBNC state. However, little is known about the genetic mechanism inducing this state. Here, we aimed to reveal the genetic determinants of the VBNC state of E. coli. We hypothesized that the VBNC state is a process wherein specific gene products important for colony formation are depleted during the extended period of stress conditions. If so, higher expression of these genes would maintain colony-forming activities, thereby restraining cells from entering the VBNC state. From an E. coli plasmid-encoded ORF library, we identified genes that were responsible for maintaining high colony-forming activities after exposure to starvation condition. Among these, cpdA encoding cAMP phosphodiesterase exhibited higher performance in the maintenance of colony-forming activities. As cpdA overexpression decreases intracellular cAMP, cAMP or its complex with cAMP-receptor protein (CRP) may negatively regulate colony-forming activities under stress conditions. We confirmed this using deletion mutants lacking adenylate cyclase or CRP. These mutants fully maintained colony-forming activities even after a long period of starvation, while wild-type cells lost most of this activity. Thus, we concluded that the lack of cAMP-CRP effectively retains high colony-forming activities, indicating that cAMP-CRP acts as a positive regulator necessary for the induction of the VBNC state in E. coli.

DOI： 10.1099/mic.0.000618

PubMed

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総ページ数：p2167〜2300   記述言語：日本語  

DOI： 10.18958/7783-00004-0006118-00

CiNii Books

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：英語   出版者・発行元：(公社)日本実験動物学会  

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記述言語：日本語   出版者・発行元：(公社)日本獣医学会  

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開催年月日： 2024年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：帯広   国名：日本国  

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開催年月日： 2024年5月

記述言語：日本語   会議種別：ポスター発表  

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開催年月日： 2024年5月

記述言語：日本語   会議種別：ポスター発表  

開催地：京都   国名：日本国  

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開催年月日： 2023年5月

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2022年9月

記述言語：日本語   会議種別：口頭発表（一般）  

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受賞区分：学会誌・学術雑誌による顕彰  受賞国：日本国

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