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"ILE"
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Structures of the ribosome bound to EF-Tu–isoleucine tRNA elucidate the mechanism of AUG avoidance
The frequency of errors upon decoding of messenger RNA by the bacterial ribosome is low, with one misreading event per 1 × 10
4
codons. In the universal genetic code, the AUN codon box specifies two amino acids, isoleucine and methionine. In bacteria and archaea, decoding specificity of the AUA and AUG codons relies on the wobble avoidance strategy that requires modification of C34 in the anticodon loop of isoleucine transfer RNA
Ile
CAU
(tRNA
Ile
CAU
). Bacterial tRNA
Ile
CAU
with 2-lysylcytidine (lysidine) at the wobble position deciphers AUA while avoiding AUG. Here we report cryo-electron microscopy structures of the
Escherichia coli
70S ribosome complexed with elongation factor thermo unstable (EF-Tu) and isoleucine-tRNA
Ile
LAU
in the process of decoding AUA and AUG. Lysidine in tRNA
Ile
LAU
excludes AUG by promoting the formation of an unusual Hoogsteen purine–pyrimidine nucleobase geometry at the third position of the codon, weakening the interactions with the mRNA and destabilizing the EF-Tu ternary complex. Our findings elucidate the molecular mechanism by which tRNA
Ile
LAU
specifically decodes AUA over AUG.
Rybak and Gagnon elucidate the mechanism of AUG codon avoidance by the minor isoleucine tRNA in
Escherichia coli
. The lysidinylated C34 in the anticodon loop of tRNA
Ile
weakens interactions with the mRNA and destabilizes the EF-Tu ternary complex.
Journal Article
Roseburia intestinalis‐derived extracellular vesicles ameliorate colitis by modulating intestinal barrier, microbiome, and inflammatory responses
Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)‐derived EVs (R‐EVs) as potent anti‐inflammatory mediators in treating dextran sulfate sodium‐induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R‐EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R‐EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile‐Pro‐Ile in the vesicular structure, R‐EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP‐1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.
Journal Article
Structural insights into the decoding capability of isoleucine tRNAs with lysidine and agmatidine
The anticodon modifications of transfer RNAs (tRNAs) finetune the codon recognition on the ribosome for accurate translation. Bacteria and archaea utilize the modified cytidines, lysidine (L) and agmatidine (agm
2
C), respectively, in the anticodon of tRNA
Ile
to decipher AUA codon. L and agm
2
C contain long side chains with polar termini, but their functions remain elusive. Here we report the cryogenic electron microscopy structures of tRNAs
Ile
recognizing the AUA codon on the ribosome. Both modifications interact with the third adenine of the codon via a unique C–A geometry. The side chains extend toward 3′ direction of the mRNA, and the polar termini form hydrogen bonds with 2′-OH of the residue 3′-adjacent to the AUA codon. Biochemical analyses demonstrated that AUA decoding is facilitated by the additional interaction between the polar termini of the modified cytidines and 2′-OH of the fourth mRNA residue. We also visualized cyclic
N
6
-threonylcarbamoyladenosine (ct
6
A), another tRNA modification, and revealed a molecular basis how ct
6
A contributes to efficient decoding.
Precise protein synthesis is achieved by tRNA modifications. Here the authors revealed that modified cytidines in tRNA
Ile
use their long side chains to make additional interactions with mRNA for stable tRNA binding on the ribosome.
Journal Article
The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition
The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNA
Ile
from tRNA
Met
solely based on the nucleotide at wobble position (N34), and a single substitution at N34 could exchange the aminoacylation specificity between two tRNAs. Here, we report the structural and biochemical mechanism of N34 recognition-based tRNA discrimination by
Saccharomyces cerevisiae
IleRS (
Sc
IleRS).
Sc
IleRS utilizes a eukaryotic/archaeal-specific arginine as the H-bond donor to recognize the common carbonyl group (H-bond acceptor) of various N34s of tRNA
Ile
, which induces mutual structural adaptations between
Sc
IleRS and tRNA
Ile
to achieve a preferable editing state. C34 of unmodified tRNA
Ile
(CAU) (behaves like tRNA
Met
) lacks a relevant H-bond acceptor, which disrupts key H-bonding interactions and structural adaptations and suspends the
Sc
IleRS·tRNA
Ile
(CAU) complex in an initial non-reactive state. This wobble nucleotide recognition-based structural adaptation provides mechanistic insights into selective tRNA aminoacylation by AARSs.
The faithful charging of amino acids to tRNAs by aminoacyl-tRNA synthetases determines protein translation fidelity. Here, the authors showed how isoleucyl-tRNA synthetase distinguishes tRNA
Ile
from tRNA
Met
based on the recognition of wobble nucleotide (N34) and subsequent structural adaptation.
Journal Article
Jasmonic Acid Signaling Pathway in Response to Abiotic Stresses in Plants
Plants as immovable organisms sense the stressors in their environment and respond to them by means of dedicated stress response pathways. In response to stress, jasmonates (jasmonic acid, its precursors and derivatives), a class of polyunsaturated fatty acid-derived phytohormones, play crucial roles in several biotic and abiotic stresses. As the major immunity hormone, jasmonates participate in numerous signal transduction pathways, including those of gene networks, regulatory proteins, signaling intermediates, and proteins, enzymes, and molecules that act to protect cells from the toxic effects of abiotic stresses. As cellular hubs for integrating informational cues from the environment, jasmonates play significant roles in alleviating salt stress, drought stress, heavy metal toxicity, micronutrient toxicity, freezing stress, ozone stress, CO2 stress, and light stress. Besides these, jasmonates are involved in several developmental and physiological processes throughout the plant life. In this review, we discuss the biosynthesis and signal transduction pathways of the JAs and the roles of these molecules in the plant responses to abiotic stresses.
Journal Article
A Member of the Arabidopsis Mitochondrial Transcription Termination Factor Family Is Required for Maturation of Chloroplast Transfer RNAIle(GAU)
Plastid gene expression is crucial for organelle function, but the factors that control it are still largely unclear. Members of the so-called mitochondrial transcription termination factor (mTERF) family are found in metazoans and plants and regulate organellar gene expression at different levels. Arabidopsis (Arabidopsis thaliana) mTERF6 is localized in chloroplasts and mitochondria, and its knockout perturbs plastid development and results in seedling lethality. In the leakymterf6-1mutant, a defect in photosynthesis is associated with reduced levels of photosystem subunits, although corresponding messenger RNA levels are unaffected, whereas translational capacity and maturation of chloroplast ribosomal RNAs (rRNAs) are perturbed inmterf6-1mutants. Bacterial one-hybrid screening, electrophoretic mobility shift assays, and coimmunoprecipitation experiments reveal a specific interaction between mTERF6 and an RNA sequence in the chloroplast isoleucine transfer RNA gene (trnI.2) located in the rRNA operon. In vitro, recombinant mTERF6 bound to its plastid DNA target site can terminate transcription. At present, it is unclear whether disturbed rRNA maturation is a primary or secondary defect. However, it is clear that mTERF6 is required for the maturation oftrnI.2. This points to an additional function of mTERFs.
Journal Article
Colonization and Community
In Colonization and Community John Belshaw takes a new look at British Columbia's first working class, the men, women, and children beneath and beyond the pit-head. Beginning with an exploration of emigrant expectations and ambitions, he investigates working conditions, household wages, racism, industrial organization, gender, schooling, leisure, community building, and the fluid identity of the British mining colony, the archetypal west coast proletariat. By connecting the story of Vancouver Island to the larger story of Victorian industrialization, he delineates what was distinctive and what was common about the lot of the settler society. Belshaw breaks new ground, challenging the easy assumptions of transferred British political traditions, analyzing the colonial at the household level, and revealing the emergent communities of Vancouver Island as the cradle of British Columbian working-class culture.
eBook
High-affinity recognition of specific tRNAs by an mRNA anticodon-binding groove
T-box riboswitches are modular bacterial noncoding RNAs that sense and regulate amino acid availability through direct interactions with tRNAs. Between the 5′ anticodon-binding stem I domain and the 3′ amino acid sensing domains of most T-boxes lies the stem II domain of unknown structure and function. Here, we report a 2.8-Å cocrystal structure of the Nocardia farcinica ileS T-box in complex with its cognate tRNAIle. The structure reveals a perpendicularly arranged ultrashort stem I containing a K-turn and an elongated stem II bearing an S-turn. Both stems rest against a compact pseudoknot, dock via an extended ribose zipper and jointly create a binding groove specific to the anticodon of its cognate tRNA. Contrary to proposed distal contacts to the tRNA elbow region, stem II locally reinforces the codon-anticodon interactions between stem I and tRNA, achieving low-nanomolar affinity. This study illustrates how mRNA junctions can create specific binding sites for interacting RNAs of prescribed sequence and structure.
Journal Article
Ripening‐induced defence signalling in Botrytis cinerea‐infected tomato fruits involves activation of ERF.F4 by a MYC2‐NOR/RIN protein complex
Summary Fleshy fruits are commercially and nutritionally important but become more susceptible to pathogens as they ripen. Active defence mechanisms continue to function in ripe fruits but they are influenced by ripening regulators and ripening outcomes. Botrytis cinerea is one of the most important fruit fungal pathogens of tomato and jasmonic acid (JA) is the major defence phytohormone involved in response to B. cinerea infection. Pathogens induce the accumulation of bioactive jasmonoyl‐isoleucine (JA‐Ile), which transmits defence signals through a hub transcription factor (TF) MYC2 that regulates defence responses. This has been clarified in depth in leaves, but how ripening, and in particular the regulators NOR and RIN influence JA‐Ile‐mediated defence responses remains unclear. In this article, we demonstrate that knocking‐out NOR or RIN either singly (CR‐NOR, CR‐RIN) or together (CR‐NOR/RIN) weakens JA‐Ile accumulation in response to B. cinerea infection in tomato fruit. Both NOR and RIN physically interact with MYC2, and 110 of 569 differentially expressed genes (DEGs) in B. cinerea‐infected wild‐type (WT) fruits were identified as direct targets of MYC2. These included ethylene response factors (ERFs) such as ERF.A2, B12, C3, F4, G2/PTI6, whose transcripts accumulated in WT but were greatly reduced in either CR‐NOR or CR‐RIN infected fruits. Only MYC2 binding to ERF.F4 was severely impaired in CR‐NOR and CR‐RIN fruits. ERF.F4 transactivates PR‐STH2 and activates defence signalling in B. cinerea‐infected fruit. The increase in susceptibility to infection caused by promotion of ripening by RIN and NOR is thus partially compensated by their positive action in defence signalling.
Journal Article