scholarly journals An early step in wobble uridine tRNA modification requires the Elongator complex

RNA ◽  
2005 ◽  
Vol 11 (4) ◽  
pp. 424-436 ◽  
Author(s):  
B. HUANG
Keyword(s):  
Trna Modification ◽  
Early Step ◽  
Elongator Complex

scholarly journals Use of a Yeast TRNase Killer Toxin to Diagnose Kti12 Motifs Required for TRNA Modification by Elongator

2017 ◽  
Author(s):  
Raffael Schaffrath ◽  
Constance Mehlgarten ◽  
Heike Prochaska ◽  
Alexander Hammermeister ◽  
Wael Abdel-Fattah ◽  
...  
Keyword(s):  
Kluyveromyces Lactis ◽  
Killer Toxin ◽  
Physical Contact ◽  
Trna Modification ◽  
Specific Chemical ◽  
Wobble Position ◽  
Elongator Complex ◽  
Partner Protein ◽  
Mutant Pool ◽  
Specific Chemical Modification

Saccharomyces cerevisiae cells are killed by zymocin, a tRNase ribotoxin complex from Kluyveromyces lactis, which cleaves anticodons and inhibits protein synthesis. Zymocin’s action requires specific chemical modification of uridine bases in the anticodon wobble position (U34) by the Elongator complex (Elp1-Elp6). Hence, loss of anticodon modification in mutants lacking Elongator or related KTI (K. lactis Toxin Insensitive) genes protects against tRNA cleavage and confers resistance to the toxin. Here, we show that zymocin can be used as a tool to genetically analyse KTI12, a gene previously shown to code for an Elongator partner protein. From a kti12 mutant pool of zymocin survivors, we identify motifs in Kti12 that are functionally directly coupled to Elongator activity. In addition, shared requirement of U34 modifications for nonsense and missense tRNA suppression (SUP4; SOE1) strongly suggests that Kti12 and Elongator cooperate to assure proper tRNA functioning. We show that the Kti12 motifs are conserved in plant ortholog DRL1/ELO4 from Arabidopsis thaliana and seem to be involved in binding of cofactors (e.g. nucleotides, calmodulin). Elongator interaction defects triggered by mutations in these motifs correlate with phenotypes typical for loss of U34 modification. Thus, tRNA modification by Elongator appears to require physical contact with Kti12, and our preliminary data suggest that metabolic signals may affect proper communication between them.

scholarly journals How Elongator Acetylates tRNA Bases

2020 ◽  
Vol 21 (21) ◽  
pp. 8209
Author(s):  
Nour-el-Hana Abbassi ◽  
Anna Biela ◽  
Sebastian Glatt ◽  
Ting-Yu Lin
Keyword(s):  
Protein Synthesis ◽  
Neurodegenerative Disorders ◽  
Trna Modification ◽  
Acetyl Coa ◽  
Translation Elongation ◽  
Transfer Rnas ◽  
Elongator Complex ◽  
Lysine Acetyltransferase ◽  
Ribosomal Translation

Elp3, the catalytic subunit of the eukaryotic Elongator complex, is a lysine acetyltransferase that acetylates the C5 position of wobble-base uridines (U34) in transfer RNAs (tRNAs). This Elongator-dependent RNA acetylation of anticodon bases affects the ribosomal translation elongation rates and directly links acetyl-CoA metabolism to both protein synthesis rates and the proteome integrity. Of note, several human diseases, including various cancers and neurodegenerative disorders, correlate with the dysregulation of Elongator’s tRNA modification activity. In this review, we focus on recent findings regarding the structure of Elp3 and the role of acetyl-CoA during its unique modification reaction.

scholarly journals SSD1 modifies phenotypes of Elongator mutants

2019 ◽  
Vol 66 (3) ◽  
pp. 481-485
Author(s):  
Fu Xu ◽  
Anders S. Byström ◽  
Marcus J. O. Johansson
Keyword(s):  
Allelic Variation ◽  
Genetic Modifier ◽  
Regulation Of Gene Expression ◽  
Yeast Cells ◽  
Trna Modification ◽  
Diverse Range ◽  
Elongator Complex ◽  
Mrna Binding Protein ◽  
Mrna Binding ◽  
Post Transcriptional Regulation

AbstractThe translational decoding properties of tRNAs are influenced by post-transcriptional modification of nucleosides in their anticodon region. The Elongator complex promotes the first step in the formation of 5-methoxycarbonylmethyl (mcm5), 5-methoxycarbonylhydroxymethyl (mchm5), and 5-carbamoylmethyl (ncm5) groups on wobble uridine residues in eukaryotic cytosolic tRNAs. Elongator mutants in yeast, worms, plants, mice, and humans not only show a tRNA modification defect, but also a diverse range of additional phenotypes. Even though the phenotypes are almost certainly caused by the reduced functionality of the hypomodified tRNAs in translation, the basis for specific phenotypes is not well understood. Here, we discuss the recent finding that the phenotypes of Saccharomyces cerevisiae Elongator mutants are modulated by the genetic background. This background-effect is largely due to the allelic variation at the SSD1 locus, which encodes an mRNA-binding protein involved in post-transcriptional regulation of gene expression. A nonsense ssd1 allele is found in several wild-type laboratory strains and the presence of this allele aggravates the stress-induced phenotypes of Elongator mutants. Moreover, other phenotypes, such as the histone acetylation and telomeric gene silencing defects, are dependent on the mutant ssd1 allele. Thus, SSD1 is a genetic modifier of the phenotypes of Elongator-deficient yeast cells.

scholarly journals Anticodon Wobble Uridine Modification by Elongator at the Crossroad of Cell Signaling, Differentiation, and Diseases

Epigenomes ◽  
2020 ◽  
Vol 4 (2) ◽  
pp. 7 ◽  
Author(s):  
Damien Hermand
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Protein Aggregation ◽  
Cell Signaling ◽  
Rna Polymerase Ii ◽  
Histone Acetyltransferase ◽  
Trna Modification ◽  
Biologically Relevant ◽  
Elongator Complex ◽  
Specific Control

First identified 20 years ago as an RNA polymerase II-associated putative histone acetyltransferase, the conserved Elongator complex has since been recognized as the central player of a complex, regulated, and biologically relevant epitranscriptomic pathway targeting the wobble uridine of some tRNAs. Numerous studies have contributed to three emerging concepts resulting from anticodon modification by Elongator: the codon-specific control of translation, the ability of reprogramming translation in various physiological or pathological contexts, and the maintenance of proteome integrity by counteracting protein aggregation. These three aspects of tRNA modification by Elongator constitute a new layer of regulation that fundamentally contributes to gene expression and are now recognized as being critically involved in various human diseases.

scholarly journals Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marija Kojic ◽  
Tomasz Gawda ◽  
Monika Gaik ◽  
Alexander Begg ◽  
Anna Salerno-Kochan ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Molecular Basis ◽  
Adaptive Functioning ◽  
Autism Spectrum ◽  
Protein Homeostasis ◽  
Trna Modification ◽  
Gene Encoding ◽  
Functional Connectome ◽  
Elongator Complex ◽  
Neurodevelopmental Phenotype

AbstractIntellectual disability (ID) and autism spectrum disorder (ASD) are the most common neurodevelopmental disorders and are characterized by substantial impairment in intellectual and adaptive functioning, with their genetic and molecular basis remaining largely unknown. Here, we identify biallelic variants in the gene encoding one of the Elongator complex subunits, ELP2, in patients with ID and ASD. Modelling the variants in mice recapitulates the patient features, with brain imaging and tractography analysis revealing microcephaly, loss of white matter tract integrity and an aberrant functional connectome. We show that the Elp2 mutations negatively impact the activity of the complex and its function in translation via tRNA modification. Further, we elucidate that the mutations perturb protein homeostasis leading to impaired neurogenesis, myelin loss and neurodegeneration. Collectively, our data demonstrate an unexpected role for tRNA modification in the pathogenesis of monogenic ID and ASD and define Elp2 as a key regulator of brain development.

scholarly journals Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification

PLoS Genetics ◽  
2011 ◽  
Vol 7 (9) ◽  
pp. e1002258 ◽  
Author(s):  
Changchun Chen ◽  
Bo Huang ◽  
Mattias Eliasson ◽  
Patrik Rydén ◽  
Anders S. Byström
Keyword(s):  
Dna Damage ◽  
Gene Silencing ◽  
Dna Damage Response ◽  
Trna Modification ◽  
Elongator Complex ◽  
Damage Response

scholarly journals Recent Advances in the Role of the Elongator Complex in Plant Physiology and tRNA Modification: A Review

2014 ◽  
Vol 13 (8) ◽  
pp. 1640-1650 ◽  
Author(s):  
Xu YAN ◽  
Xiao-huan JIN ◽  
You-mei WANG ◽  
Bo ZHENG ◽  
Peng CHEN
Keyword(s):  
Plant Physiology ◽  
Trna Modification ◽  
Elongator Complex ◽  
Recent Advances

Inhibition of ADP-Induced Responses in Human Platelets by Agents Elevating the Cyclic AMP Level: Comparison of Aggregation and Shape Change

1984 ◽  
Vol 52 (03) ◽  
pp. 333-335 ◽  
Author(s):  
Vider M Steen ◽  
Holm Holmsen
Keyword(s):  
Inhibitory Action ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Shape Change ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Inhibitory Effects ◽  
Early Step ◽  
Stimulus Response ◽  
Sequential Relationship

SummaryThe inhibitory effect of cAMP-elevating agents on shape change and aggregation in human platelets was studied to improve the understanding of the sequential relationship between these two responses.Human platelet-rich plasma was preincubated for 2 min at 37° C with prostaglandin E1 or adenosine, agents known to elevate the intracellular level of cAMP. Their inhibitory effects on ADP-induced shape change and aggregation were determined both separately and simultaneously. The dose-inhibition patterns for shape change and aggregation were similar for both PGE1 and adenosine. There was no distinct difference between the inhibitory action of these two inhibitors.These observations suggest that elevation of the intracellular concentration of cAMP interferes with an early step in the stimulus-response coupling that is common for aggregation and shape change.

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