scholarly journals LncRNA GIRGL drives CAPRIN1-mediated phase separation to suppress glutaminase-1 translation under glutamine deprivation

2021 ◽  
Vol 7 (13) ◽  
pp. eabe5708
Author(s):  
Ruijie Wang ◽  
Leixi Cao ◽  
Rick Francis Thorne ◽  
Xu Dong Zhang ◽  
Jinming Li ◽  
...  
Keyword(s):  
Phase Separation ◽  
Noncoding Rna ◽  
Mrna Translation ◽  
Granule Formation ◽  
Carbon And Nitrogen ◽  
Rate Limiting Step ◽  
Glutamine Deprivation ◽  
Underlying Mechanisms ◽  
Rate Limiting ◽  
Glutaminase 1

Glutamine constitutes an essential source of both carbon and nitrogen for numerous biosynthetic processes. The first and rate-limiting step of glutaminolysis involves the generation of glutamate from glutamine, catalyzed by glutaminase-1 (GLS1). Shortages of glutamine result in reductions in GLS1, but the underlying mechanisms are not fully known. Here, we characterize a long noncoding RNA, GIRGL (glutamine insufficiency regulator of glutaminase lncRNA), that is induced upon glutamine starvation. Manipulating GIRGL revealed a relationship between its expression and the translational suppression of GLS1. Cellular GIRGL levels are balanced by a combination of transactivation by c-JUN together with negative stability regulation via HuR/Ago2. Increased levels of GIRGL in the absence of glutamine drive formation of a complex between dimers of CAPRIN1 and GLS1 mRNA, serving to promote liquid-liquid phase separation of CAPRIN1 and inducing stress granule formation. Suppressing GLS1 mRNA translation enables cancer cells to survive under prolonged glutamine deprivation stress.

scholarly journals Compelling Evidence Suggesting the Codon Usage of SARS-CoV-2 Adapts to Human After the Split From RaTG13

2021 ◽  
Vol 17 ◽  
pp. 117693432110520
Author(s):  
Yanping Zhang ◽  
Xiaojie Jin ◽  
Haiyan Wang ◽  
Yaoyao Miao ◽  
Xiaoping Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Codon Usage ◽  
Synonymous Codon ◽  
Mrna Translation ◽  
Synonymous Codon Usage ◽  
Fast Decoding ◽  
Rate Limiting Step ◽  
Human Lungs ◽  
Human Sample ◽  
Rate Limiting

SARS-CoV-2 needs to efficiently make use of the resources from hosts in order to survive and propagate. Among the multiple layers of regulatory network, mRNA translation is the rate-limiting step in gene expression. Synonymous codon usage usually conforms with tRNA concentration to allow fast decoding during translation. It is acknowledged that SARS-CoV-2 has adapted to the codon usage of human lungs so that the virus could rapidly proliferate in the lung environment. While this notion seems to nicely explain the adaptation of SARS-CoV-2 to lungs, it is unable to tell why other viruses do not have this advantage. In this study, we retrieve the GTEx RNA-seq data for 30 tissues (belonging to over 17 000 individuals). We calculate the RSCU (relative synonymous codon usage) weighted by gene expression in each human sample, and investigate the correlation of RSCU between the human tissues and SARS-CoV-2 or RaTG13 (the closest coronavirus to SARS-CoV-2). Lung has the highest correlation of RSCU to SARS-CoV-2 among all tissues, suggesting that the lung environment is generally suitable for SARS-CoV-2. Interestingly, for most tissues, SARS-CoV-2 has higher correlations with the human samples compared with the RaTG13-human correlation. This difference is most significant for lungs. In conclusion, the codon usage of SARS-CoV-2 has adapted to human lungs to allow fast decoding and translation. This adaptation probably took place after SARS-CoV-2 split from RaTG13 because RaTG13 is less perfectly correlated with human. This finding depicts the trajectory of adaptive evolution from ancestral sequence to SARS-CoV-2, and also well explains why SARS-CoV-2 rather than other viruses could perfectly adapt to human lung environment.

Regulation of Protein Synthesis by eIF4E in the Brain

2020 ◽  
Author(s):  
Kleanthi Chalkiadaki ◽  
Stella Kouloulia ◽  
Clive R. Bramham ◽  
Christos G. Gkogkas
Keyword(s):  
Protein Synthesis ◽  
Brain Function ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Eukaryotic Mrnas ◽  
Rate Limiting ◽  
The Brain ◽  
Key Pathways

Regulation of gene expression at the level of mRNA translation is crucial for all the functions our brains carry out. eIF4E binds to the 5′-end of eukaryotic mRNAs and dictates the rate-limiting step of cap-dependent initiation. This chapter reviews the key pathways regulating eIF4E function, but also the less studied and novel mechanisms of eIF4E modulation, linked to synaptic plasticity, learning and memory, and nervous system disorders. Understanding how regulation of protein synthesis by eIF4E affects different aspects of brain function is yet elusive.

scholarly journals The role of mammalian poly(A)-binding proteins in co-ordinating mRNA turnover

2012 ◽  
Vol 40 (4) ◽  
pp. 856-864 ◽  
Author(s):  
Matthew Brook ◽  
Nicola K. Gray
Keyword(s):  
Recent Progress ◽  
Binding Proteins ◽  
Mrna Translation ◽  
Mrna Turnover ◽  
Cis Acting ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Mrna Transcripts ◽  
Rate Limiting

The function of cytoplasmic PABPs [poly(A)-binding proteins] in promoting mRNA translation has been intensively studied. However, PABPs also have less clearly defined functions in mRNA turnover including roles in default deadenylation, a major rate-limiting step in mRNA decay, as well as roles in the regulation of mRNA turnover by cis-acting control elements and in the detection of aberrant mRNA transcripts. In the present paper, we review our current understanding of the complex roles of PABP1 in mRNA turnover, focusing on recent progress in mammals and highlighting some of the major questions that remain to be addressed.

Ornithine Decarboxylase Activity in Cultured Endothelial Cells Stimulated by Serum, Thrombin and Serotonin

1978 ◽  
Vol 39 (02) ◽  
pp. 496-503 ◽  
Author(s):  
P A D’Amore ◽  
H B Hechtman ◽  
D Shepro
Keyword(s):  
Endothelial Cells ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Aortic Endothelial Cells ◽  
Ornithine Decarboxylase Activity ◽  
Rate Limiting Step ◽  
Bovine Aortic Endothelial Cells ◽  
Limiting Step ◽  
Rate Limiting ◽  
Serum Serotonin

SummaryOrnithine decarboxylase (ODC) activity, the rate-limiting step in the synthesis of polyamines, can be demonstrated in cultured, bovine, aortic endothelial cells (EC). Serum, serotonin and thrombin produce a rise in ODC activity. The serotonin-induced ODC activity is significantly blocked by imipramine (10-5 M) or Lilly 11 0140 (10-6M). Preincubation of EC with these blockers together almost completely depresses the 5-HT-stimulated ODC activity. These observations suggest a manner by which platelets may maintain EC structural and metabolic soundness.

Dynamics of hepatic and peripheral insulin effects suggest common rate-limiting step in vivo

Diabetes ◽  
1993 ◽  
Vol 42 (2) ◽  
pp. 296-306 ◽  
Author(s):  
D. C. Bradley ◽  
R. A. Poulin ◽  
R. N. Bergman
Keyword(s):  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

Cobalt/Lewis Acid Catalysis for Hydrocarbofunctionalization of Alkynes via Cooperative C–H Activation

2020 ◽  
Author(s):  
Chang-Sheng Wang ◽  
Sabrina Monaco ◽  
Anh Ngoc Thai ◽  
Md. Shafiqur Rahman ◽  
Chen Wang ◽  
...  
Keyword(s):  
Catalytic System ◽  
Lewis Acid ◽  
Hydrogen Transfer ◽  
Acid Catalysis ◽  
Rate Limiting Step ◽  
Site Selectivity ◽  
Set Up ◽  
Site Selective ◽  
First Time ◽  
Rate Limiting

A catalytic system comprised of a cobalt-diphosphine complex and a Lewis acid (LA) such as AlMe3 has been found to promote hydrocarbofunctionalization reactions of alkynes with Lewis basic and electron-deficient substrates such as formamides, pyridones, pyridines, and azole derivatives through site-selective C-H activation. Compared with known Ni/LA catalytic system for analogous transformations, the present catalytic system not only feature convenient set up using inexpensive and bench-stable precatalyst and ligand such as Co(acac)3 and 1,3-bis(diphenylphosphino)propane (dppp), but also display distinct site-selectivity toward C-H activation of pyridone and pyridine derivatives. In particular, a completely C4-selective alkenylation of pyridine has been achieved for the first time. Mechanistic stidies including DFT calculations on the Co/Al-catalyzed addition of formamide to alkyne have suggested that the reaction involves cleavage of the carbamoyl C-H bond as the rate-limiting step, which proceeds through a ligand-to-ligand hydrogen transfer (LLHT) mechanism leading to an alkyl(carbamoyl)cobalt intermediate.

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