• BMB Reports
• /
• 제50권4호
• /
• pp.194-200
• /
• 2017

Eukaryotic gene expression is precisely regulated at all points between transcription and translation. In this review, we focus on translational control mediated by the 3'-untranslated regions (UTRs) of mRNAs. mRNA 3'-UTRs contain cis-acting elements that function in the regulation of protein translation or mRNA decay. Each RNA binding protein that binds to these cis-acting elements regulates mRNA translation via various mechanisms targeting the mRNA cap structure, the eukaryotic initiation factor 4E (eIF4E)-eIF4G complex, ribosomes, and the poly (A) tail. We also discuss translation-mediated regulation of mRNA fate.

• BMB Reports
• /
• 제53권2호
• /
• pp.94-99
• /
• 2020

Brain cytoplasmic 200 RNA (BC200 RNA) is proposed to act as a local translational modulator by inhibiting translation after being targeted to neuronal dendrites. However, the mechanism by which BC200 RNA inhibits translation is not fully understood. Although a detailed functional analysis of RNA motifs is essential for understanding the BC200 RNA-mediated translation-inhibition mechanism, there is little relevant research on the subject. Here, we performed a systematic domain-dissection analysis of BC200 RNA to identify functional RNA motifs responsible for its translational-inhibition activity. Various RNA variants were assayed for their ability to inhibit translation of luciferase mRNA in vitro. We found that the 111-200-nucleotide region consisting of part of the Alu domain as well as the A/C-rich domain (consisting of both the A-rich and C-rich domains) is most effective for translation inhibition. Surprisingly, we also found that individual A-rich, A/C-rich, and Alu domains can enhance translation but at different levels for each domain, and that these enhancing effects manifest as cap-dependent translation.

• Molecules and Cells
• /
• 제24권3호
• /
• pp.445-451
• /
• 2007

Translation initiation factor 4E (eIF4E) is a key regulator of protein synthesis. Abnormal regulation of eIF4E is closely linked to oncogenic transformation. Several regulatory mechanisms affecting eIF4E are discussed, including transcriptional regulation, phosphorylation and binding of an inhibitor protein. However it is not clear how the level of eIF4E protein is regulated under basal conditions. Here we demonstrate that Diap1 (Drosophila Inhibitor of Apoptosis Protein), a cell death inhibitor, binds directly to eIF4E and poly-ubiquitinates it via its E3 ligase activity, promoting its proteasome-dependent degradation. Expression of Diap1 caused a reduction of Cyclin D1 protein level and inhibited the growth stimulation induced by overexpression of eIF4E. Taken together, our results suggest that the level of eIF4E protein is regulated by Diap1, and that IAPs may play a role in cap-dependent translation by regulating the level of eIF4E protein.

• BMB Reports
• /
• 제49권4호
• /
• pp.199-200
• /
• 2016

Gene regulation in the brain is essential for long-term plasticity and memory formation. Despite this established notion, the quantitative translational map in the brain during memory formation has not been reported. To systematically probe the changes in protein synthesis during memory formation, our recent study exploited ribosome profiling using the mouse hippocampal tissues at multiple time points after a learning event. Analysis of the resulting database revealed novel types of gene regulation after learning. First, the translation of a group of genes was rapidly suppressed without change in mRNA levels. At later time points, the expression of another group of genes was downregulated through reduction in mRNA levels. This reduction was predicted to be downstream of inhibition of ESR1 (Estrogen Receptor 1) signaling. Overexpressing Nrsn1, one of the genes whose translation was suppressed, or activating ESR1 by injecting an agonist interfered with memory formation, suggesting the functional importance of these findings. Moreover, the translation of genes encoding the translational machineries was found to be suppressed, among other genes in the mouse hippocampus. Together, this unbiased approach has revealed previously unidentified characteristics of gene regulation in the brain and highlighted the importance of repressive controls.

• BMB Reports
• /
• 제30권1호
• /
• pp.55-59
• /
• 1997

The heat shock response is a universal stress response observed in all organisms and cultured cells. The response is regulated at both the transcriptional and translational level. Heat shocked Drosophila melanogaster Kc cells are used as the system for the study of translational regulation. In this system non-heat shock messages are associated with polysome but are not translated in a heat shocked condition. To figure out the change in the translation machinery. the effects of translation elongation inhibitors were tested on Kc cells. The result showed that the sensitivity of translation to these drugs changed in heat shocked cells. The significant changes were the decreased inhibition of heat shock protein synthesis by cycloheximide, emetine. and puromycin. and the increased inhibition of heat shock protein synthesis by verrucarin A. implying that the translation elongation mechanism in heat shocked cells changed.

• Molecules and Cells
• /
• 제39권12호
• /
• pp.841-846
• /
• 2016

Local protein synthesis mediates precise spatio-temporal regulation of gene expression for neuronal functions such as long-term plasticity, axon guidance and regeneration. To reveal the underlying mechanisms of local translation, it is crucial to understand mRNA transport, localization and translation in live neurons. Among various techniques for mRNA analysis, fluorescence microscopy has been widely used as the most direct method to study localization of mRNA. Live-cell imaging of single RNA molecules is particularly advantageous to dissect the highly heterogeneous and dynamic nature of messenger ribonucleoprotein (mRNP) complexes in neurons. Here, we review recent advances in the study of mRNA localization and translation in live neurons using novel techniques for single-RNA imaging.

• BMB Reports
• /
• 제50권11호
• /
• pp.539-545
• /
• 2017

The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated $eIF2{\alpha}$ kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor $eIF2{\alpha}$. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes.

• 대한감각통합치료학회지
• /
• 제20권3호
• /
• pp.27-37
• /
• 2022

목적 : 본 연구는 Sensory Processing and Self-Regulation Checklist(SPSRC)의 국내사용을 위해 한국어로 번안하고 내용타당도를 알아보기 위해 검증을 실시하였다. 연구방법 : 내용타당도를 검증하기 위해 번역, 내용 적합성 검증, 역번역, 번역 검증 위원회, 내용 이해도 검증의 과정을 거쳐 완성된 한글판 SPSRC를 작업치료학과 교수 3명과 작업치료사 7명에게 제시하여 내용 타당도 지수(Content Validity Index; CVI)를 확인하였다. 결과 : 한글판 SPSRC의 내용 타당도 지수(CVI)는 130문항 모두 .90 이상이었다. 또한 전체 문항의 CVI 역시 .99로 높은 수준의 내용타당도 결과를 나타냈다. 결론 : 한글판 SPSRC는 아동의 감각처리능력과 자기조절능력을 함께 측정할 수 있는 도구로서 높은 내용 타당도를 가진 것으로 확인되었다. 한글판 SPSRC는 임상에서 아동의 감각처리능력과 자기조절능력에 대한 이해와 평가를 용이하게 하며, 감각통합 중재 계획을 위해 활용할 수 있을 것으로 기대한다.

• BMB Reports
• /
• 제47권11호
• /
• pp.619-624
• /
• 2014

Antisense RNA is a type of noncoding RNA (ncRNA) that binds to complementary mRNA sequences and induces gene repression by inhibiting translation or degrading mRNA. Recently, several small ncRNAs (sRNAs) have been identified in Escherichia coli that act as antisense RNA mainly via base pairing with mRNA. The base pairing predominantly leads to gene repression, and in some cases, gene activation. In the current study, we examined how the location of target sites affects sRNA-mediated gene regulation. An efficient antisense RNA expression system was developed, and the effects of antisense RNAs on various target sites in a model mRNA were examined. The target sites of antisense RNAs suppressing gene expression were identified, not only in the translation initiation region (TIR) of mRNA, but also at the junction between the coding region and 3' untranslated region. Surprisingly, an antisense RNA recognizing the upstream region of TIR enhanced gene expression through increasing mRNA stability.

• 통합자연과학논문집
• /
• 제12권4호
• /
• pp.127-132
• /
• 2019

Programmed cell death 4 (PDCD4) is a novel tumor suppressor that function in the nucleus and the cytoplasm and appears to be involved in the regulation of transcription and translation. Stress granules (SGs) are cytoplasmic foci at which untranslated mRNAs accumulate when cells exposed to environmental stresses. Since PDCD4 has implicated in translation repression through direct interaction with eukaryotic translation initiation factor 4A (eIF4A), we here investigated if PDCD4 has a functional role in the process of SG assembly under oxidative stresses. Using immunofluorescence microscopy, we found that PDCD4 is localized to SGs under oxidative stresses. Next, we tested if knockdown of PDCD4 has an effect on the assembly of SG using PDCD4-specific siRNA. Interestingly, SG assembly was accelerated and this effect was caused by sensitization of phosphorylation of eIF2α and dephosphorylation of eIF4E binding protein (4E-BP). These results suggest that PDCD4 has an effect on SG dynamics and possibly involved in cap-dependent translation repression under stress conditions.