Adaptation to Overflow Metabolism by Mutations That Impair tRNA Modification in Experimentally Evolved Bacteria.

When microbes grow in foreign nutritional environments, selection may enrich mutations in unexpected pathways connecting growth and homeostasis. An evolution experiment designed to identify beneficial mutations in Burkholderia cenocepacia captured six independent nonsynonymous substitutions in the essential gene , which modifies tRNA by adding a lysine to the anticodon for faithful AUA recognition. Further, five additional mutants acquired mutations in tRNA, which strongly suggests that disrupting the TilS-tRNA interaction was subject to strong positive selection.

The neuroscience of positive emotions and affect: Implications for cultivating happiness and wellbeing.

This review paper provides an integrative account regarding neurophysiological correlates of positive emotions and affect that cumulatively contribute to the scaffolding for happiness and wellbeing in humans and other animals. This paper reviews the associations among neurotransmitters, hormones, brain networks, and cognitive functions in the context of positive emotions and affect. Consideration of lifespan developmental perspectives are incorporated, and we also examine the impact of healthy social relationships and environmental contexts on the modulation of positive emotions and affect.

A Novel Aminoacyl-tRNA Synthetase Appended Domain Can Supply the Core Synthetase with Its Amino Acid Substrate.

The structural organization and functionality of aminoacyl-tRNA synthetases have been expanded through polypeptide additions to their core aminoacylation domain. We have identified a novel domain appended to the methionyl-tRNA synthetase (MetRS) of the intracellular pathogen . Sequence analysis of this N-terminal region suggests the appended domain is an aminotransferase, which we demonstrate here.

Trauma, Resilience, and Mental Health in Migrant and Non-Migrant Youth: An International Cross-Sectional Study Across Six Countries.

Resilience is a dynamic process of positive adaptation to significant adversity. While there has been substantial focus on risks and negative outcomes associated with youth migrancy, there is limited evidence of the relationship between the adversity of migration, and resilience, wellbeing, and positive mental health in adolescents. This international study aimed to explore the differences in resilience, wellbeing, and mental health behaviors in migrant and non-migrant adolescents tested across six countries (Australia, New Zealand, UK, China, South Africa, and Canada) with varying levels of trauma exposure.

Putting amino acids onto tRNAs: The aminoacyl-tRNA synthetases as catalysts.

In this chapter we consider the catalytic approaches used by aminoacyl-tRNA synthetase (AARS) enzymes to synthesize aminoacyl-tRNA from cognate amino acid and tRNA. This ligase reaction proceeds through an activated aminoacyl-adenylate (aa-AMP). Common themes among AARSs include use of induced fit to drive catalysis and transition state stabilization by class-conserved sequence and structure motifs.

Bacterial wobble modifications of NNA-decoding tRNAs.

Nucleotides of transfer RNAs (tRNAs) are highly modified, particularly at the anticodon. Bacterial tRNAs that read A-ending codons are especially notable. The U34 nucleotide canonically present in these tRNAs is modified by a wide range of complex chemical constituents.

Structure and Dynamics of tRNA Containing Core Substitutions.

The fidelity of protein synthesis is largely dominated by the accurate recognition of transfer RNAs (tRNAs) by their cognate aminoacyl-tRNA synthetases. Aminoacylation of each tRNA with its cognate amino acid is necessary to maintain the accuracy of genetic code input. Aminoacylated tRNA functions in both initiation and elongation steps during protein synthesis.

11th IUBMB Focused Meeting on the Aminoacyl-tRNA Synthetases: Sailing a New Sea of Complex Functions in Human Biology and Disease.

The 11th IUBMB Focused Meeting on Aminoacyl-tRNA Synthetases was held in Clearwater Beach, Florida from 29 October⁻2 November 2017, with the aim of presenting the latest research on these enzymes and promoting interchange among aminoacyl-tRNA synthetase (ARS) researchers. Topics covered in the meeting included many areas of investigation, including ARS evolution, mechanism, editing functions, biology in prokaryotic and eukaryotic cells and their organelles, their roles in human diseases, and their application to problems in emerging areas of synthetic biology. In this report, we provide a summary of the major themes of the meeting, citing contributions from the oral presentations in the meeting.

MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery.

While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. Throughout the review, we briefly discuss important historical events to provide a context for how far the field has progressed over the past few decades.

Evidence for late resolution of the aux codon box in evolution.

Recognition strategies for tRNA aminoacylation are ancient and highly conserved, having been selected very early in the evolution of the genetic code. In most cases, the trinucleotide anticodons of tRNA are important identity determinants for aminoacylation by cognate aminoacyl-tRNA synthetases. However, a degree of ambiguity exists in the recognition of certain tRNA(Ile) isoacceptors that are initially transcribed with the methionine-specifying CAU anticodon.

Curcumin aggravates CNS pathology in experimental systemic lupus erythematosus.

Complement activation and inflammation are key disease features of systemic lupus erythematosus. Curcumin is an anti-inflammatory agent that inhibits the complement cascade. Therefore, we hypothesized that curcumin will be protective in CNS lupus.

Sex differences in the use of delayed semantic context when listening to disrupted speech.

Female as opposed to male listeners were better able to use a delayed informative cue at the end of a long sentence to report an earlier word which was disrupted by noise. Informative (semantically related) or uninformative (semantically unrelated) word cues were presented 2, 6, or 10 words after a target word whose initial phoneme had been replaced with noise. A total of 84 young adults (45 males) listened to each sentence and then repeated it after its offset.

Mitochondrial aminoacyl-tRNA synthetase single-nucleotide polymorphisms that lead to defects in refolding but not aminoacylation.

Defects in organellar translation are the underlying cause of a number of mitochondrial diseases, including diabetes, deafness, encephalopathy, and other mitochondrial myopathies. The most common causes of these diseases are mutations in mitochondria-encoded tRNAs. It has recently become apparent that mutations in nuclear-encoded components of the mitochondrial translation machinery, such as aminoacyl-tRNA synthetases (aaRSs), can also lead to disease.

Misacylation of specific nonmethionyl tRNAs by a bacterial methionyl-tRNA synthetase.

Aminoacyl-tRNA synthetases perform a critical step in translation by aminoacylating tRNAs with their cognate amino acids. Although high fidelity of aminoacyl-tRNA synthetases is often thought to be essential for cell biology, recent studies indicate that cells tolerate and may even benefit from tRNA misacylation under certain conditions. For example, mammalian cells selectively induce mismethionylation of nonmethionyl tRNAs, and this type of misacylation contributes to a cell's response to oxidative stress.

Role for a conserved structural motif in assembly of a class I aminoacyl-tRNA synthetase active site.

The catalytic domains of class I aminoacyl-tRNA synthetases are built around a conserved Rossmann nucleotide binding fold, with additional polypeptide domains responsible for tRNA binding or hydrolytic editing of misacylated substrates. Structural comparisons identified a conserved motif bridging the catalytic and anticodon binding domains of class Ia and Ib enzymes. This stem contact fold (SCF) has been proposed to globally orient each enzyme's cognate tRNA by interacting with the inner corner of the L-shaped tRNA.

Experimental and computational determination of tRNA dynamics.

As the molecular representation of the genetic code, tRNA plays a central role in the translational machinery where it interacts with several proteins and other RNAs during the course of protein synthesis. These interactions exploit the dynamic flexibility of tRNA. In this minireview, we discuss the effects of modified bases, ions, and proteins on tRNA structure and dynamics and the challenges of observing its motions over the cycle of translation.

Effect of a domain-spanning disulfide on aminoacyl-tRNA synthetase activity.

Enzymes regulated by allostery undergo conformational rearrangement upon binding effector molecules. For modular proteins, a flexible interface may mediate reorientation of the protein domains and transmit binding events to activate catalysis at a distance. Aminoacyl-tRNA synthetases (aaRSs) that use tRNA anticodons as identity elements can be considered allosteric enzymes in which aminoacylation of the tRNA acceptor stem is enhanced upon anticodon binding.

An operational RNA code for faithful assignment of AUG triplets to methionine.

The assignment of AUG codons to methionine remains a central question of the evolution of the genetic code. We have unveiled a strategy for the discrimination among tRNAs containing CAU (AUG-decoding) anticodons. Mycoplasma penetrans methionyl-tRNA synthetase can directly differentiate between tRNA(Ile)(CAU) and tRNA(Met)(CAU) transcripts (a recognition normally achieved through the modification of anticodon bases).

Using molecular dynamics to map interaction networks in an aminoacyl-tRNA synthetase.

Long-range functional communication is a hallmark of many enzymes that display allostery, or action-at-a-distance. Many aminoacyl-tRNA synthetases can be considered allosteric, in that their trinucleotide anticodons bind the enzyme at a site removed from their catalytic domains. Such is the case with E.

Mutational analysis of the Escherichia coli DEAD box protein CsdA.

The Escherichia coli cold shock protein CsdA is a member of the DEAD box family of ATP-dependent RNA helicases, which share a core of nine conserved motifs. The DEAD (Asp-Glu-Ala-Asp) motif for which this family is named has been demonstrated to be essential for ATP hydrolysis. We show here that CsdA exhibits in vitro ATPase and helicase activities in the presence of short RNA duplexes with either 3' or 5' extensions at 15 degrees C.

DNA minor groove adducts formed by a platinum-acridine conjugate inhibit association of tata-binding protein with its cognate sequence.

PT-ACRAMTU ([PtCl(en)(ACRAMTU-S)](NO(3))(2), en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a cytotoxic platinum-acridine conjugate previously shown to form adducts with the N3 endocyclic nitrogen of adenine in the DNA minor groove. This unusual observation and our prior determination of the pronounced 5'-TA/TA base-step affinity of the drug have prompted us to investigate effects of these adducts on DNA minor groove binding proteins. Here, we used electrophoretic mobility shift assays to study the recognition of a PT-ACRAMTU-modified TATA box sequence by TATA-binding protein (TBP).