The Role of the Universally Conserved ATPase YchF/Ola1 in Translation Regulation during Cellular Stress

The ability to respond to metabolic or environmental changes is an essential feature in all cells and involves both transcriptional and translational regulators that adjust the metabolic activity to fluctuating conditions. While transcriptional regulation has been studied in detail, the important role of the ribosome as an additional player in regulating gene expression is only beginning to emerge. Ribosome-interacting proteins are central to this translational regulation and include universally conserved ribosome interacting proteins, such as the ATPase YchF (Ola1 in eukaryotes). In both eukaryotes and bacteria, the cellular concentrations of YchF/Ola1 determine the ability to cope with different stress conditions and are linked to several pathologies in humans. The available data indicate that YchF/Ola1 regulates the stress response via controlling non-canonical translation initiation and via protein degradation. Although the molecular mechanisms appear to be different between bacteria and eukaryotes, increased non-canonical translation initiation is a common consequence of YchF/Ola1 regulated translational control in E. coli and H. sapiens. In this review, we summarize recent insights into the role of the universally conserved ATPase YchF/Ola1 in adapting translation to unfavourable conditions.

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The Role of Translation Initiation Regulation in Haematopoiesis

Comparative and Functional Genomics ◽

10.1155/2012/576540 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Godfrey Grech ◽

Marieke von Lindern

Keyword(s):

Gene Expression ◽

Translation Initiation ◽

Translational Control ◽

Molecular Mechanisms ◽

Rna Binding ◽

Regulation Of Gene Expression ◽

Mrna Translation ◽

Translation Control ◽

Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

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Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽

10.1093/glycob/cwaa110 ◽

2020 ◽

Author(s):

Kaitlyn A Dorsett ◽

Michael P Marciel ◽

Jihye Hwang ◽

Katherine E Ankenbauer ◽

Nikita Bhalerao ◽

...

Keyword(s):

Cancer Cells ◽

Translational Regulation ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Sialic Acids ◽

Invasion Resistance ◽

Cell Behaviors ◽

Molecular Events ◽

Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

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CREB mediates the C. elegans dauer polyphenism through direct and cell-autonomous regulation of TGF-β expression

PLoS Genetics ◽

10.1371/journal.pgen.1009678 ◽

2021 ◽

Vol 17 (7) ◽

pp. e1009678

Author(s):

JiSoo Park ◽

Hyekyoung Oh ◽

Do-Young Kim ◽

YongJin Cheon ◽

Yeon-Ji Park ◽

...

Keyword(s):

Developmental Plasticity ◽

Molecular Mechanisms ◽

Environmental Changes ◽

Marker Gene ◽

Camp Response Element Binding ◽

Camp Response Element ◽

Developmental Programs ◽

C Elegans ◽

Element Binding Protein

Animals can adapt to dynamic environmental conditions by modulating their developmental programs. Understanding the genetic architecture and molecular mechanisms underlying developmental plasticity in response to changing environments is an important and emerging area of research. Here, we show a novel role of cAMP response element binding protein (CREB)-encoding crh-1 gene in developmental polyphenism of C. elegans. Under conditions that promote normal development in wild-type animals, crh-1 mutants inappropriately form transient pre-dauer (L2d) larva and express the L2d marker gene. L2d formation in crh-1 mutants is specifically induced by the ascaroside pheromone ascr#5 (asc-ωC3; C3), and crh-1 functions autonomously in the ascr#5-sensing ASI neurons to inhibit L2d formation. Moreover, we find that CRH-1 directly binds upstream of the daf-7 TGF-β locus and promotes its expression in the ASI neurons. Taken together, these results provide new insight into how animals alter their developmental programs in response to environmental changes.

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Role of medicinal plants against neurodegenerative diseases

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210211123539 ◽

2021 ◽

Vol 22 ◽

Author(s):

Ritika Luthra ◽

Arpita Roy

Keyword(s):

Medicinal Plants ◽

Neurodegenerative Diseases ◽

Molecular Mechanisms ◽

Environmental Changes ◽

Inflammatory Responses ◽

Vital Role ◽

Significant Loss ◽

Therapeutic Interventions ◽

Inflammatory Stress

: Diseases with a significant loss of neurons, structurally and functionally are termed as neurodegenerative diseases. Due to the present therapeutic interventions and progressive nature of diseases, a variety of side effects have risen up, thus leading the patients to go for an alternative medication. The role of medicinal plants in such cases has been beneficial because of their exhibition via different cellular and molecular mechanisms. Alleviation in inflammatory responses, suppression of the functionary aspect of pro-inflammatory cytokines like a tumor, improvement in antioxidative properties is among few neuroprotective mechanisms of traditional plants. Variation in transcription and transduction pathways play a vital role in the preventive measures of plants in such diseases. Neurodegenerative diseases are generally caused by depletion of proteins, oxidative and inflammatory stress, environmental changes and so on, with aging being the most important cause. Natural compounds can be used in order to treat neurodegenerative diseases Medicinal plants such as Ginseng, Withania somnifera, Bacopa monnieri, Ginkgo biloba, etc. are some of the medicinal plants for prevention of neurological symptoms. This review deals with the use of different medicinal plants for the prevention of neurodegenerative diseases.

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uORFs: Important Cis-Regulatory Elements in Plants

International Journal of Molecular Sciences ◽

10.3390/ijms21176238 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6238

Author(s):

Ting Zhang ◽

Anqi Wu ◽

Yaping Yue ◽

Yu Zhao

Keyword(s):

Gene Expression ◽

Translation Initiation ◽

Translational Control ◽

Translational Regulation ◽

Regulatory Elements ◽

Ribosome Profiling ◽

Open Reading Frames ◽

Post Translational Modification ◽

Cis Acting ◽

Eukaryotic Mrnas

Gene expression is regulated at many levels, including mRNA transcription, translation, and post-translational modification. Compared with transcriptional regulation, mRNA translational control is a more critical step in gene expression and allows for more rapid changes of encoded protein concentrations in cells. Translation is highly regulated by complex interactions between cis-acting elements and trans-acting factors. Initiation is not only the first phase of translation, but also the core of translational regulation, because it limits the rate of protein synthesis. As potent cis-regulatory elements in eukaryotic mRNAs, upstream open reading frames (uORFs) generally inhibit the translation initiation of downstream major ORFs (mORFs) through ribosome stalling. During the past few years, with the development of RNA-seq and ribosome profiling, functional uORFs have been identified and characterized in many organisms. Here, we review uORF identification, uORF classification, and uORF-mediated translation initiation. More importantly, we summarize the translational regulation of uORFs in plant metabolic pathways, morphogenesis, disease resistance, and nutrient absorption, which open up an avenue for precisely modulating the plant growth and development, as well as environmental adaption. Additionally, we also discuss prospective applications of uORFs in plant breeding.

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The HOG Pathway Dictates the Short-Term Translational Response after Hyperosmotic Shock

Molecular Biology of the Cell ◽

10.1091/mbc.e10-01-0006 ◽

2010 ◽

Vol 21 (17) ◽

pp. 3080-3092 ◽

Cited By ~ 57

Author(s):

Jonas Warringer ◽

Malin Hult ◽

Sergi Regot ◽

Francesc Posas ◽

Per Sunnerhagen

Keyword(s):

Translational Control ◽

Ribosomal Proteins ◽

Translational Regulation ◽

Environmental Changes ◽

Transcriptional Response ◽

Fine Tuning ◽

Yeast Cells ◽

Adaptive Responses ◽

Hog Pathway ◽

Hyperosmotic Shock

Cellular responses to environmental changes occur on different levels. We investigated the translational response of yeast cells after mild hyperosmotic shock by isolating mRNA associated with multiple ribosomes (polysomes) followed by array analysis. Globally, recruitment of preexisting mRNAs to ribosomes (translational response) is faster than the transcriptional response. Specific functional groups of mRNAs are recruited to ribosomes without any corresponding increase in total mRNA. Among mRNAs under strong translational up-regulation upon shock, transcripts encoding membrane-bound proteins including hexose transporters were enriched. Similarly, numerous mRNAs encoding cytoplasmic ribosomal proteins run counter to the overall trend of down-regulation and are instead translationally mobilized late in the response. Surprisingly, certain transcriptionally induced mRNAs were excluded from ribosomal association after shock. Importantly, we verify, using constructs with intact 5′ and 3′ untranslated regions, that the observed changes in polysomal mRNA are reflected in protein levels, including cases with only translational up-regulation. Interestingly, the translational regulation of the most highly osmostress-regulated mRNAs was more strongly dependent on the stress-activated protein kinases Hog1 and Rck2 than the transcriptional regulation. Our results show the importance of translational control for fine tuning of the adaptive responses.

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Established and Emerging Regulatory Roles of Eukaryotic Translation Initiation Factor 5B (eIF5B)

Frontiers in Genetics ◽

10.3389/fgene.2021.737433 ◽

2021 ◽

Vol 12 ◽

Author(s):

Prakash Amruth Raj Chukka ◽

Stacey D. Wetmore ◽

Nehal Thakor

Keyword(s):

Translation Initiation ◽

Translational Control ◽

Translational Regulation ◽

Eukaryotic Cell ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Eukaryotic Translation ◽

Cellular Mrnas ◽

Eukaryotic Translation Initiation ◽

Initiation Stage

Translational control (TC) is one the crucial steps that dictate gene expression and alter the outcome of physiological process like programmed cell death, metabolism, and proliferation in a eukaryotic cell. TC occurs mainly at the translation initiation stage. The initiation factor eIF5B tightly regulates global translation initiation and facilitates the expression of a subset of proteins involved in proliferation, inhibition of apoptosis, and immunosuppression under stress conditions. eIF5B enhances the expression of these survival proteins to allow cancer cells to metastasize and resist chemotherapy. Using eIF5B as a biomarker or drug target could help with diagnosis and improved prognosis, respectively. To achieve these goals, it is crucial to understand the role of eIF5B in translational regulation. This review recapitulates eIF5B’s regulatory roles in the translation initiation of viral mRNA as well as the cellular mRNAs in cancer and stressed eukaryotic cells.

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Molecular studies into cell biological role of Copine-4 in Retinal Ganglion Cells

PLoS ONE ◽

10.1371/journal.pone.0255860 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0255860

Author(s):

Manvi Goel ◽

Angel M. Aponte ◽

Graeme Wistow ◽

Tudor C. Badea

Keyword(s):

Retinal Ganglion Cells ◽

Molecular Mechanisms ◽

Ganglion Cells ◽

Mass Spectrometry Analysis ◽

Hek293 Cells ◽

Retinal Cell ◽

Interacting Proteins ◽

Retinal Ganglion ◽

Over Expression

The molecular mechanisms underlying morphological diversity in retinal cell types are poorly understood. We have previously reported that several members of the Copine family of Ca-dependent membrane adaptors are expressed in Retinal Ganglion Cells and transcriptionally regulated by Brn3 transcription factors. Several Copines are enriched in the retina and their over-expression leads to morphological changes -formation of elongated processes-, reminiscent of neurites, in HEK293 cells. However, the role of Copines in the retina is largely unknown. We now investigate Cpne4, a Copine whose expression is restricted to Retinal Ganglion Cells. Over-expression of Cpne4 in RGCs in vivo led to formation of large varicosities on the dendrites but did not otherwise visibly affect dendrite or axon formation. Protein interactions studies using yeast two hybrid analysis from whole retina cDNA revealed two Cpne4 interacting proteins–Host Cell Factor 1 and Morn2. Mass Spectrometry analysis of retina lysate pulled down using Cpne4 or its vonWillebrand A domain showed 207 interacting proteins. A Gene Ontology analysis of the discovered proteins suggests that Cpne4 is involved in several metabolic and signaling pathways in the retina.

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The Role of Light and Circadian Clock in Regulation of Leaf Senescence

Frontiers in Plant Science ◽

10.3389/fpls.2021.669170 ◽

2021 ◽

Vol 12 ◽

Author(s):

Juhyeon Lee ◽

Myeong Hoon Kang ◽

Jung Yeon Kim ◽

Pyung Ok Lim

Keyword(s):

Circadian Clock ◽

Leaf Senescence ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Environmental Changes ◽

Control Plant ◽

Structural Features ◽

Clock Period ◽

Environmental Signals

Leaf senescence is an integrated response of the cells to develop age information and various environmental signals. Thus, some of the genes involved in the response to environmental changes are expected to regulate leaf senescence. Light acts not only as the primary source of energy for photosynthesis but also as an essential environmental cue that directly control plant growth and development including leaf senescence. The molecular mechanisms linking light signaling to leaf senescence have recently emerged, exploring the role of Phytochrome-Interacting Factors (PIFs) as a central player leading to diverse senescence responses, senescence-promoting gene regulatory networks (GRNs) involving PIFs, and structural features of transcription modules in GRNs. The circadian clock is an endogenous time-keeping system for the adaptation of organisms to changing environmental signals and coordinates developmental events throughout the life of the plant. Circadian rhythms can be reset by environmental signals, such as light-dark or temperature cycles, to match the environmental cycle. Research advances have led to the discovery of the role of core clock components as senescence regulators and their underlying signaling pathways, as well as the age-dependent shortening of the circadian clock period. These discoveries highlight the close relationship between the circadian system and leaf senescence. Key issues remain to be elucidated, including the effect of light on leaf senescence in relation to the circadian clock, and the identification of key molecules linking aging, light, and the circadian clock, and integration mechanisms of various senescence-affecting signals at the multi-regulation levels in dynamics point of view.

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Comprehensive Genome-Wide Approaches to Activity-Dependent Translational Control in Neurons

International Journal of Molecular Sciences ◽

10.3390/ijms21051592 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1592

Author(s):

Han Kyoung Choe ◽

Jun Cho

Keyword(s):

Gene Expression ◽

Translational Control ◽

Translational Regulation ◽

Molecular Mechanisms ◽

Regulation Of Gene Expression ◽

Autism Spectrum ◽

Specific Stimulus ◽

Genome Wide ◽

Activity Dependent ◽

The Brain

Activity-dependent regulation of gene expression is critical in experience-mediated changes in the brain. Although less appreciated than transcriptional control, translational control is a crucial regulatory step of activity-mediated gene expression in physiological and pathological conditions. In the first part of this review, we overview evidence demonstrating the importance of translational controls under the context of synaptic plasticity as well as learning and memory. Then, molecular mechanisms underlying the translational control, including post-translational modifications of translation factors, mTOR signaling pathway, and local translation, are explored. We also summarize how activity-dependent translational regulation is associated with neurodevelopmental and psychiatric disorders, such as autism spectrum disorder and depression. In the second part, we highlight how recent application of high-throughput sequencing techniques has added insight into genome-wide studies on translational regulation of neuronal genes. Sequencing-based strategies to identify molecular signatures of the active neuronal population responding to a specific stimulus are discussed. Overall, this review aims to highlight the implication of translational control for neuronal gene regulation and functions of the brain and to suggest prospects provided by the leading-edge techniques to study yet-unappreciated translational regulation in the nervous system.

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