scholarly journals Author Correction: Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them

2018 ◽  
Vol 19 (10) ◽  
pp. 673-673 ◽  
Author(s):  
Kathrin Leppek ◽  
Rhiju Das ◽  
Maria Barna
Keyword(s):  
Translation Regulation ◽  
Eukaryotic Translation

scholarly journals Regulation of eIF2α Phosphorylation by MAPKs Influences Polysome Stability and Protein Translation

2021 ◽  
Author(s):  
Sana Parveen ◽  
Haripriya Parthasarathy ◽  
Dhiviya Vedagiri ◽  
Divya Gupta ◽  
Hitha Gopalan Nair ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Protein Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Translation Regulation ◽  
Eukaryotic Translation ◽  
Eif2α Phosphorylation ◽  
Mitogen Activated Protein ◽  
Eukaryotic Translation Initiation ◽  
Polysome Stability

Regulation of protein translation occurs primarily at the level of initiation and is mediated by multiple signaling pathways, majorly mechanistic target of rapamycin complex 1 (mTORC1), mitogen-activated protein kinases (MAPKs), and the eukaryotic translation initiation factor eIF2. While mTORC1 and eIF2α influence the polysome stability, MAPKs influence the phosphorylation of the cap-binding protein eIF4E and are known to influence translation of only a small set of mRNAs. Here, we demonstrate that p38 MAPK and ERK1/2 regulate translation through integrated stress response (ISR) pathways. Dual inhibition (dual-Mi) of p38 MAPK and ERK1/2 caused substantial phosphorylation of eIF2α in a synergistic manner, resulting in near-absolute collapse of polysomes. This regulation was independent of Mnk1/2, a well-studied mediator of translation regulation by the MAPKs. Dual-Mi-induced polysome dissociation was far more striking than that caused by sodium arsenite, a strong inducer of ISR. Interestingly, induction of ISR caused increased p38 phosphorylation, and its inhibition resulted in stronger polysome dissociation, indicating the importance of p38 in the translation activities. Thus, our studies demonstrate a major, unidentified role for ERK1/2 and more particularly p38 MAPK in the maintenance of homeostasis of polysome association and translation activities.

scholarly journals Autonomous functionality of an upstream open reading frame in polycistronic mammalian mRNAs

2018 ◽  
Author(s):  
Shohei Kitano ◽  
Gabriel Pratt ◽  
Keizo Takao ◽  
Yasunori Aizawa
Keyword(s):  
Brain Regions ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Upstream Open Reading Frame ◽  
Translation Regulation ◽  
Reading Frame ◽  
Eukaryotic Translation ◽  
Upstream Open Reading Frames ◽  
Human And Mouse ◽  
Reading Frames

SUMMARYUpstream open reading frames (uORFs) are established as cis-acting elements for eukaryotic translation of annotated ORFs (anORFs) located on the same mRNAs. Here, we identified a mammalian uORF with functions that are independent from anORF translation regulation. Bioinformatics screening using ribosome profiling data of human and mouse brains yielded 308 neurologically vital genes from which anORF and uORFs are polycistronically translated in both species. Among them, Arhgef9 contains a uORF named SPICA, which is highly conserved among vertebrates and stably translated only in specific brain regions of mice. Disruption of SPICA translation by ATG-to-TAG substitutions did not perturb translation or function of its anORF product, collybistin. SPICA-null mice displayed abnormal maternal reproductive performance and enhanced anxiety-like behavior, characteristic of ARHGEF9-associated neurological disorders. This study demonstrates that mammalian uORFs can be independent genetic units, revising the prevailing dogma of the monocistronic gene in mammals, and even eukaryotes.

scholarly journals MNK-eIF4E signalling is a highly conserved mechanism for sensory neuron axonal plasticity: evidence from Aplysia californica

2019 ◽  
Vol 374 (1785) ◽  
pp. 20190289 ◽  
Author(s):  
Sandra M. Mihail ◽  
Andi Wangzhou ◽  
Kumud K. Kunjilwar ◽  
Jamie K. Moy ◽  
Gregory Dussor ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Therapeutic Potential ◽  
Aplysia Californica ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Mitogen Activated Protein Kinase ◽  
Initiation Factor ◽  
Translation Regulation ◽  
Eukaryotic Translation

Injury to sensory neurons causes an increase in the excitability of these cells leading to enhanced action potential generation and a lowering of spike threshold. This type of sensory neuron plasticity occurs across vertebrate and invertebrate species and has been linked to the development of both acute and persistent pain. Injury-induced plasticity in sensory neurons relies on localized changes in gene expression that occur at the level of mRNA translation. Many different translation regulation signalling events have been defined and these signalling events are thought to selectively target subsets of mRNAs. Recent evidence from mice suggests that the key signalling event for nociceptor plasticity is mitogen-activated protein kinase-interacting kinase (MNK) -mediated phosphorylation of eukaryotic translation initiation factor (eIF) 4E. To test the degree to which this is conserved in other species, we used a previously described sensory neuron plasticity model in Aplysia californica . We find, using a variety of pharmacological tools, that MNK signalling is crucial for axonal hyperexcitability in sensory neurons from Aplysia . We propose that MNK-eIF4E signalling is a core, evolutionarily conserved, signalling module that controls nociceptor plasticity. This finding has important implications for the therapeutic potential of this target, and it provides interesting clues about the evolutionary origins of mechanisms important for pain-related plasticity. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

scholarly journals Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation

2016 ◽  
Vol 113 (30) ◽  
pp. 8466-8471 ◽  
Author(s):  
Celestino Velásquez ◽  
Erdong Cheng ◽  
Masahiro Shuda ◽  
Paula J. Lee-Oesterreich ◽  
Lisa Pogge von Strandmann ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Mammalian Target Of Rapamycin ◽  
Mrna Translation ◽  
T Antigen ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Translation Regulation ◽  
Viral Oncoprotein ◽  
Eukaryotic Translation ◽  
Small T Antigen

Mammalian target of rapamycin (mTOR)-directed eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation promotes cap-dependent translation and tumorigenesis. During mitosis, cyclin-dependent kinase 1 (CDK1) substitutes for mTOR and fully phosphorylates 4E-BP1 at canonical sites (T37, T46, S65, and T70) and the noncanonical S83 site, resulting in a mitosis-specific hyperphosphorylated δ isoform. Colocalization studies with a phospho-S83 specific antibody indicate that 4E-BP1 S83 phosphorylation accumulates at centrosomes during prophase, peaks at metaphase, and decreases through telophase. Although S83 phosphorylation of 4E-BP1 does not affect general cap-dependent translation, expression of an alanine substitution mutant 4E-BP1.S83A partially reverses rodent cell transformation induced by Merkel cell polyomavirus small T antigen viral oncoprotein. In contrast to inhibitory mTOR 4E-BP1 phosphorylation, these findings suggest that mitotic CDK1-directed phosphorylation of δ-4E-BP1 may yield a gain of function, distinct from translation regulation, that may be important in tumorigenesis and mitotic centrosome function.

Impact of microRNAs on molecular epidemiology

2011 ◽  
Vol 152 (16) ◽  
pp. 633-641 ◽  
Author(s):  
Katalin Gőcze ◽  
Katalin Gombos ◽  
Gábor Pajkos ◽  
Ingrid Magda ◽  
Ágoston Ember ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Cancer Research ◽  
Molecular Epidemiology ◽  
Wide Spectrum ◽  
Translation Regulation ◽  
Rna Sequences ◽  
Serum Mirna ◽  
The Past ◽  
Non Coding Rna ◽  
Free Serum

Cancer research concerning short non-coding RNA sequences and functionally linked to RNA interference (RNAi) have reached explosive breakthrough in the past decade. Molecular technology applies microRNA in extremely wide spectrum from molecular tumor prediction, diagnostics, progression monitoring and prevention. Functional analysis of tissue miRNA and cell-free serum miRNA in posttranscription and translation regulation innovated and restructured the knowledge on the field. This review focuses on molecular epidemiology and primary prevention aspects of the small non-coding RNA sequences. Orv. Hetil., 2011, 152, 633–641.

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