scholarly journals METTL1 promotes hepatocarcinogenesis via m 7 G tRNA modification‐dependent translation control

2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Zhihang Chen ◽  
Wanjie Zhu ◽  
Shenghua Zhu ◽  
Kaiyu Sun ◽  
Junbin Liao ◽  
...  
Keyword(s):  
Trna Modification ◽  
Translation Control

scholarly journals Local Protein Translation and RNA Processing of Synaptic Proteins in Autism Spectrum Disorder

2021 ◽  
Vol 22 (6) ◽  
pp. 2811
Author(s):  
Yuyoung Joo ◽  
David R. Benavides
Keyword(s):  
Autism Spectrum Disorder ◽  
Fragile X ◽  
Single Gene ◽  
Protein Translation ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Synaptic Proteins ◽  
Local Translation ◽  
Translation Control

Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition associated with impairments in social interaction, communication and repetitive behaviors. While the underlying disease mechanisms remain to be fully elucidated, dysfunction of neuronal plasticity and local translation control have emerged as key points of interest. Translation of mRNAs for critical synaptic proteins are negatively regulated by Fragile X mental retardation protein (FMRP), which is lost in the most common single-gene disorder associated with ASD. Numerous studies have shown that mRNA transport, RNA metabolism, and translation of synaptic proteins are important for neuronal health, synaptic plasticity, and learning and memory. Accordingly, dysfunction of these mechanisms may contribute to the abnormal brain function observed in individuals with autism spectrum disorder (ASD). In this review, we summarize recent studies about local translation and mRNA processing of synaptic proteins and discuss how perturbations of these processes may be related to the pathophysiology of ASD.

scholarly journals Exploiting RNA thermometer-driven molecular bioprocess control as a concept for heterologous rhamnolipid production

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philipp Noll ◽  
Chantal Treinen ◽  
Sven Müller ◽  
Lars Lilge ◽  
Rudolf Hausmann ◽  
...  
Keyword(s):  
High Titer ◽  
Production Capacity ◽  
Batch Process ◽  
Product Formation ◽  
Effect Of Temperature ◽  
Industrial Biotechnology ◽  
Temperature Sensitive ◽  
Translation Control ◽  
Rhamnolipid Production ◽  
Rna Thermometer

AbstractA key challenge to advance the efficiency of bioprocesses is the uncoupling of biomass from product formation, as biomass represents a by-product that is in most cases difficult to recycle efficiently. Using the example of rhamnolipid biosurfactants, a temperature-sensitive heterologous production system under translation control of a fourU RNA thermometer from Salmonella was established to allow separating phases of preferred growth from product formation. Rhamnolipids as bulk chemicals represent a model system for future processes of industrial biotechnology and are therefore tied to the efficiency requirements in competition with the chemical industry. Experimental data confirms function of the RNA thermometer and suggests a major effect of temperature on specific rhamnolipid production rates with an increase of the average production rate by a factor of 11 between 25 and 38 °C, while the major part of this increase is attributable to the regulatory effect of the RNA thermometer rather than an unspecific overall increase in bacterial metabolism. The production capacity of the developed temperature sensitive-system was evaluated in a simple batch process driven by a temperature switch. Product formation was evaluated by efficiency parameters and yields, confirming increased product formation rates and product-per-biomass yields compared to a high titer heterologous rhamnolipid production process from literature.

scholarly journals Correction to article ‘Iron–sulfur biology invades tRNA modification: the case of U34 sulfuration’

2021 ◽  
Author(s):  
Jingjing Zhou ◽  
Marine Lénon ◽  
Jean-Luc Ravanat ◽  
Nadia Touati ◽  
Christophe Velours ◽  
...  
Keyword(s):  
Trna Modification ◽  
Iron Sulfur

scholarly journals Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability

2021 ◽  
Vol 7 (13) ◽  
pp. eabf3072
Author(s):  
Y. Nagayoshi ◽  
T. Chujo ◽  
S. Hirata ◽  
H. Nakatsuka ◽  
C.-W. Chen ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
State Level ◽  
Memory Deficits ◽  
Ribosome Profiling ◽  
Translation Efficiency ◽  
Trna Modification ◽  
Synaptic Organization ◽  
Transfer Rnas ◽  
The Brain

FtsJ RNA 2′-O-methyltransferase 1 (FTSJ1) gene has been implicated in X-linked intellectual disability (XLID), but the molecular pathogenesis is unknown. We show that Ftsj1 is responsible for 2′-O-methylation of 11 species of cytosolic transfer RNAs (tRNAs) at the anticodon region, and these modifications are abolished in Ftsj1 knockout (KO) mice and XLID patient–derived cells. Loss of 2′-O-methylation in Ftsj1 KO mouse selectively reduced the steady-state level of tRNAPhe in the brain, resulting in a slow decoding at Phe codons. Ribosome profiling showed that translation efficiency is significantly reduced in a subset of genes that need to be efficiently translated to support synaptic organization and functions. Ftsj1 KO mice display immature synaptic morphology and aberrant synaptic plasticity, which are associated with anxiety-like and memory deficits. The data illuminate a fundamental role of tRNA modification in the brain through regulation of translation efficiency and provide mechanistic insights into FTSJ1-related XLID.

scholarly journals Robotic Precisely Oocyte Blind Enucleation Method

2021 ◽  
Vol 11 (4) ◽  
pp. 1850
Author(s):  
Xiangfei Zhao ◽  
Maosheng Cui ◽  
Yidi Zhang ◽  
Yaowei Liu ◽  
Xin Zhao
Keyword(s):  
Success Rate ◽  
Nuclear Transfer ◽  
Operation Time ◽  
Volume Control ◽  
Translation Control ◽  
Cleavage Rate ◽  
Training Time ◽  
Manual Method ◽  
Control Oocyte ◽  
Key Techniques

Oocyte enucleation is a critical procedure for somatic cell nuclear transfer. Yet, the main steps of oocyte enucleation are still manually operated, which presents several drawbacks such as low precision, high repetition error, and long training time for operators. For improving the operation efficiency and success rate, a robotic precise oocyte blind enucleation method is presented in this paper. The proposed method involves the following key techniques: oocyte translation control, oocyte immobilization and penetration control, and enucleation volume control based on the adaptive slide mode. Compared with the manual blind enucleation method, the proposed robotic blind enucleation method reduced the operation time by 44.5% (manual method: 62 s vs. proposed method: 34.4 s), increased the accuracy of enucleation by 83.1% (manual method: 30.7 vs. proposed method: 5.2), increased the success rate from 80% to 93.3%, and increased the cleavage rate from 41.7% to 63.3%.

Making sense of mRNA landscapes: Translation control in neurodevelopment

2021 ◽  
Author(s):  
Yongkyu Park ◽  
Nicholas Page ◽  
Iva Salamon ◽  
Diana Li ◽  
Mladen‐Roko Rasin
Keyword(s):  
Translation Control ◽  
Making Sense

scholarly journals Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

2021 ◽  
Vol 22 (7) ◽  
pp. 3463
Author(s):  
Chia-Hung Lin ◽  
Chen-Chung Liao ◽  
Mei-Yu Chen ◽  
Teh-Ying Chou
Keyword(s):  
Molecular Mechanisms ◽  
Mrna Level ◽  
Feedback Regulation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Physiology ◽  
Hydroxyl Groups ◽  
Post Translational Modification ◽  
Translation Control ◽  
Glcnac Transferase

Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

scholarly journals Ionizing Radiation and Translation Control: A Link to Radiation Hormesis?

2020 ◽  
Vol 21 (18) ◽  
pp. 6650
Author(s):  
Usha Kabilan ◽  
Tyson E. Graber ◽  
Tommy Alain ◽  
Dmitry Klokov
Keyword(s):  
Protein Synthesis ◽  
Ionizing Radiation ◽  
Molecular Mechanisms ◽  
Low Dose ◽  
Mrna Translation ◽  
Cellular Responses ◽  
Translation Control ◽  
Cis Acting ◽  
Radiation Hormesis ◽  
Downstream Signaling

Protein synthesis, or mRNA translation, is one of the most energy-consuming functions in cells. Translation of mRNA into proteins is thus highly regulated by and integrated with upstream and downstream signaling pathways, dependent on various transacting proteins and cis-acting elements within the substrate mRNAs. Under conditions of stress, such as exposure to ionizing radiation, regulatory mechanisms reprogram protein synthesis to translate mRNAs encoding proteins that ensure proper cellular responses. Interestingly, beneficial responses to low-dose radiation exposure, known as radiation hormesis, have been described in several models, but the molecular mechanisms behind this phenomenon are largely unknown. In this review, we explore how differences in cellular responses to high- vs. low-dose ionizing radiation are realized through the modulation of molecular pathways with a particular emphasis on the regulation of mRNA translation control.

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