Translation articles within Nature Communications

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  • Article
    | Open Access

    Jaako et al. discover a conserved tier of translational control that dynamically couples ribosome assembly and recycling. This mechanism is corrupted in an inherited bone marrow failure disorder associated with an increased risk of blood cancer.

    • Pekka Jaako
    • , Alexandre Faille
    •  & Alan J. Warren
  • Article
    | Open Access

    For decades, miRNAs have been studied primarily by ensemble methods, where a bulk collection of molecules is measured outside cells. Here, Kobayashi and Singer report methods to image miRNA function at the single-molecule level inside cells.

    • Hotaka Kobayashi
    •  & Robert H. Singer
  • Article
    | Open Access

    Understanding the mechanisms of SARS-CoV-2 infection is important to control the pandemic. Here the authors show the biological and pathological role of RNA G-quadruplex structure in both SARS-CoV-2 genome and host factors, particularly TMPRSS2.

    • Geng Liu
    • , Wenya Du
    •  & Xianghui Fu
  • Article
    | Open Access

    The biogenesis of nuclear pores imposes a logistic challenge for cells. Here, the authors investigate structural motifs for co-translational interactions in nucleoporins and find that co-translational assembly events differ between paralogous assembly pathways thus contributing to faithful assembly.

    • Maximilian Seidel
    • , Anja Becker
    •  & Martin Beck
  • Article
    | Open Access

    Rebelo-Guiomar et al. unveil late stage assembly intermediates of the human mitochondrial ribosome by inactivating the methyltransferase MRM2 in cells. Absence of MRM2 impairs organismal homeostasis, while its catalytic activity is dispensable for mitoribosomal biogenesis.

    • Pedro Rebelo-Guiomar
    • , Simone Pellegrino
    •  & Michal Minczuk
  • Article
    | Open Access

    The cell cycle regulates translation during mitosis by controlling DENR stability. Here, the authors show the non-canonical translation initiation complex DENR·MCTS1 is phosphorylated during mitosis by CDK1 and 2, enabling the translation of genes needed for proper mitotic progression.

    • Katharina Clemm von Hohenberg
    • , Sandra Müller
    •  & Aurelio A. Teleman
  • Article
    | Open Access

    Combined methylmalonic acidemia (MMA) and hyperhomocysteinemias are inborn errors of vitamin B12 metabolism, and mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) underlie some forms of these disorders. Here the authors generated mouse models of a human syndrome due to mutations in RONIN (THAP11) and HCFC1, and show that this syndrome is both an inborn error of vitamin B12 metabolism and displays some features of ribosomopathy.

    • Tiffany Chern
    • , Annita Achilleos
    •  & Ross A. Poché
  • Article
    | Open Access

    Genome editing methods are limited by the inability to selectively edit repetitive sequences. Here the authors demonstrate precise editing of a repetitive genetic element, a ribosome, while avoiding edits to native sites sharing identical sequence.

    • Felix Radford
    • , Shane D. Elliott
    •  & Farren J. Isaacs
  • Article
    | Open Access

    EF-G drives ribosomal translocation along mRNA. Time-resolved cryo-EM captured translocation with EF-G•GTP—without inhibitors—revealing how EF-G uses ribosome fluctuations to drive translocation and GTP hydrolysis to leave at the right moment.

    • Christine E. Carbone
    • , Anna B. Loveland
    •  & Andrei A. Korostelev
  • Article
    | Open Access

    Programmed ribosomal frameshifting (PRF) occurs in many viruses including SARS-CoV-2 to allow the translation of multiple proteins from a single transcript. Here, the authors identify the human short isoform of the zinc-finger antiviral protein (ZAP-S) as a direct regulator of PRF in SARS-CoV-2 that severely impairs SARS-CoV-2 frameshifting in cells and directly interacts with the SARS-CoV-2 RNA; interfering with the folding of the frameshift RNA element.

    • Matthias M. Zimmer
    • , Anuja Kibe
    •  & Neva Caliskan
  • Article
    | Open Access

    Mitoribosomes are remarkably diverse in their structures and compositions. Here the authors combine biochemistry, genetics, single particle cryo-electron microscopy and in situ cryo-electron tomography to reveal the mitochondrial ribosome of Chlamydomonas reinhardtii as an extreme example of evolution and species-specific adaptation.

    • Florent Waltz
    • , Thalia Salinas-Giegé
    •  & Yaser Hashem
  • Article
    | Open Access

    Many RNA viruses employ programmed –1 ribosomal frameshifting (PRF) to expand their coding capacity and optimize production of viral proteins. Here, the authors report structural and biophysical analysis of protein 2A from a cardiovirus, with insights into the mechanism of its PRF-stimulatory function.

    • Chris H. Hill
    • , Lukas Pekarek
    •  & Ian Brierley
  • Article
    | Open Access

    Here the authors show that a viral protein interferes with the binding of phosphorylated eIF2 to eIF2B, thereby suppressing the host integrated stress response (ISR). This suppression of the ISR abrogates translational changes of the host and ameliorates neurite degradation under stress.

    • Kazuhiro Kashiwagi
    • , Yuichi Shichino
    •  & Takuhiro Ito
  • Article
    | Open Access

    Cilia are microtubule-based organelles containing proteins transported from the cell body. Here, the authors show that the multicilia of mouse ependymal cells contain ribosomal components, tubulin mRNA,18 S rRNA and nascent tubulin peptides, suggesting local translation in the ciliary compartment.

    • Kai Hao
    • , Yawen Chen
    •  & Xueliang Zhu
  • Article
    | Open Access

    The differentiation of naive T cells to immune suppressing induced regulatory T (iTreg) cells requires TGF-beta-1 and downregulation of mTORC1 activity, which inhibits mRNA translation. Here the authors show that iTreg cell differentiation uses an alternate mRNA translation mechanism involving translation factors DAP5 and eIF3d.

    • Viviana Volta
    • , Sandra Pérez-Baos
    •  & Robert J. Schneider
  • Article
    | Open Access

    Processing bodies are phase separated compartments enriched in translationally repressed mRNAs. Here, Smith et al. show that, in sensory neurons, eukaryotic elongation factor 2 kinase (eEF2K) plays key roles in the regulation of processing body abundance and the formation of translationally inactive ribosomes.

    • Patrick R. Smith
    • , Sarah Loerch
    •  & Zachary T. Campbell
  • Article
    | Open Access

    Start codon selection is commonly thought to occur through the unidirectional scanning of the mRNA by the 40 S ribosome. Here the authors provide evidence that the pre-initiation complex can backslide on the mRNA to initiate translation at upstream AUG codons.

    • Yifei Gu
    • , Yuanhui Mao
    •  & Shu-Bing Qian
  • Article
    | Open Access

    To characterize molecular changes during cell type transitions, the authors develop a method to simultaneously measure protein expression and thermal stability changes. They apply this approach to study differences between human pluripotent stem cells, their progenies, parental and allogeneic cells.

    • Pierre Sabatier
    • , Christian M. Beusch
    •  & Roman A. Zubarev
  • Article
    | Open Access

    Alpha-1-antitrypsin (AAT) deficiency results from misfolding-prone AAT variants. Here the authors show that AAT forms co-translational folding intermediates on the ribosome that persist upon release and determine its folding fate. They show too that the ribosome can also modulate misfolding-prone AAT intermediates during their synthesis.

    • Elena Plessa
    • , Lien P. Chu
    •  & Lisa D. Cabrita
  • Article
    | Open Access

    It is increasingly recognised that the spatial localisation of RNA is important for proper cellular function. Here, the authors investigate RNA localisation in skeletal muscle and develop methods to show that global active transport of RNA is required to maintain dispersion of gene products in the large muscle syncytium.

    • Lance T. Denes
    • , Chase P. Kelley
    •  & Eric T. Wang
  • Article
    | Open Access

    Movement of the ribosome along an mRNA requires the universally-conserved translocase (EF-G in bacteria) that couples GTP hydrolysis to directed movement. Here the authors use time-resolved Cryo-EM to visualize the GTPase-powered step on native translocating ribosomes and capture key translocation intermediates.

    • Valentyn Petrychenko
    • , Bee-Zen Peng
    •  & Niels Fischer
  • Article
    | Open Access

    Genetic code expansion strategies are limited to specific codons that can be reassigned to new amino acids. Here the authors show that quadruplet-decoding tRNAs (qtRNAs) can be rapidly discovered and evolved to decode new quadruplet codons, enabling four independent decoding events in a single protein in living cells.

    • Erika A. DeBenedictis
    • , Gavriela D. Carver
    •  & Ahmed H. Badran
  • Article
    | Open Access

    Here, the authors use in vivo site-specific crosslinking to provide molecular-level insight into how the fungal Hsp70 chaperone system — the Ssb:Ssz1:Zuo1 triad — assists the folding process for the nascent peptide chain emerging from the ribosome tunnel.

    • Kanghyun Lee
    • , Thomas Ziegelhoffer
    •  & Elizabeth A. Craig
  • Article
    | Open Access

    Bacteria adjust the expression of some of their metabolic enzymes through metabolite-sensing ribosome nascent chain complexes. Here the authors present a cryo-EM structure of an E. coli ribosome stalled during translation of the TnaC leader peptide and propose a model for L-Trp dependent ribosome stalling where L-Trp competes with release factor 2 for binding to the TnaC-ribosome complex.

    • Anne-Xander van der Stel
    • , Emily R. Gordon
    •  & C. Axel Innis
  • Article
    | Open Access

    Here, Kim et al. apply various sequencing techniques (RPF-seq, QTI-seq, mRNA-seq, sRNA-seq) to unravel the high-resolution, longitudinal translatome and transcriptome of SARS-CoV-2. They identify a translation initiation site in the leader sequence of all genomic and subgenomic RNAs and show its relevance for the SARS-CoV-2 translatome.

    • Doyeon Kim
    • , Sukjun Kim
    •  & Daehyun Baek
  • Article
    | Open Access

    Ribosome profiling has become the gold standard to analyze mRNA translation dynamics, and the translation inhibitor cycloheximide (CHX) is often used in its application. Here the authors systematically demonstrate that CHX does not bias the outcome of ribosome profiling experiments in most organisms.

    • Puneet Sharma
    • , Jie Wu
    •  & Sebastian A. Leidel
  • Article
    | Open Access

    Shwachman-Diamond syndrome (SDS) is a leukemia predisposition disorder that is caused by defective release of eIF6 during ribosome assembly. Here the authors show that acquired somatic EIF6 mutations are frequent in the hematopoietic cells from individuals with SDS and provide a selective advantage over non-modified cells.

    • Shengjiang Tan
    • , Laëtitia Kermasson
    •  & Patrick Revy
  • Article
    | Open Access

    Skeletal muscle stem cells (or satellite cells, SCs) are normally quiescent but activate and expand in response to injury. Here the authors show that induction of DHX36 helicase during SC activation promotes mRNA translation by binding to 5′UTR mRNA G-quadruplexes (rG4) in targets including Gnai2 and unwinding them.

    • Xiaona Chen
    • , Jie Yuan
    •  & Huating Wang
  • Article
    | Open Access

    Trans-translation, mediated by small protein B (SmpB) and transfer-messenger RNA (tmRNA), enables recycling of the ribosomes stalled on defective mRNAs in bacteria. Here, the authors report structures of the ribosome during trans-translation that reveal a translocation intermediate and elucidate the movements of the tmRNA-SmpB complex in the ribosome.

    • Charlotte Guyomar
    • , Gaetano D’Urso
    •  & Reynald Gillet
  • Article
    | Open Access

    Translational frameshifting is a mechanism that expands the coding capabilities of mRNA. Here, structures of 70S ribosome complexes with GTPase elongation factor G (EF-G), a +1-frameshifting-prone mRNA and tRNAs reveal the cooperation between the ribosome and EF-G to induce +1 frameshifting during the translocation step.

    • Gabriel Demo
    • , Howard B. Gamper
    •  & Andrei A. Korostelev
  • Article
    | Open Access

    Assembly of the mitoribosome requires assistance from numerous specialized factors. Here, structures of the human 39S late assembly intermediates identify several assembly factors which keep the 16S rRNA in immature conformations, and reveal deacylated tRNA in the ribosomal E-site, suggesting a role in 39S assembly.

    • Jingdong Cheng
    • , Otto Berninghausen
    •  & Roland Beckmann
  • Article
    | Open Access

    Mutations in 5’ untranslated regions (UTRs) have a functional role in gene expression in cancer. Here, the authors develop a sequencing-based high throughput functional assay named PLUMAGE and show the effects of these mutations on gene expression and their association with clinical outcomes in prostate cancer.

    • Yiting Lim
    • , Sonali Arora
    •  & Andrew C. Hsieh
  • Article
    | Open Access

    Here, the authors report de novo design, optimization and characterization of tRNAs that decode UGA stop codons in E. coli. The structure of the ribosome in a complex with the designed tRNA bound to a UGA stop codon suggests that distinct A-site ligands (tRNAs versus release factors) induce distinct conformation of the stop codon within the mRNA in the decoding center.

    • Suki Albers
    • , Bertrand Beckert
    •  & Zoya Ignatova
  • Article
    | Open Access

    Mitochondrial ribosomes (mitoribosomes) are characterized by a distinct architecture and thus biogenesis pathway. Here, cryo-EM structures of mitoribosome large subunit assembly intermediates elucidate final steps of 16 S rRNA folding, methylation and peptidyl transferase centre (PTC) completion, as well as functions of several mitoribosome assembly factors.

    • Miriam Cipullo
    • , Genís Valentín Gesé
    •  & Joanna Rorbach
  • Article
    | Open Access

    Maturation of the ribosomal peptidyl transferase center (PTC) is mediated by universally conserved GTPases. Here, cryo-EM structures of mitochondrial ribosomal large subunit assembly intermediates and of mature ribosomes offer insight into the roles of several assembly factors, including GTPBP6’s role in both ribosome biogenesis and recycling.

    • Hauke S. Hillen
    • , Elena Lavdovskaia
    •  & Ricarda Richter-Dennerlein
  • Article
    | Open Access

    Mammalian mitoribosomes feature dramatically reduced ribosomal RNAs and follow mitochondria specific assembly pathways. Here the authors describe the process of human mitochondrial ribosome maturation that results in the formation of the ribosomal active site region, including the peptidyl transferase loop and the two tRNA-binding loops.

    • Tea Lenarčič
    • , Mateusz Jaskolowski
    •  & Nenad Ban
  • Article
    | Open Access

    High-resolution cryo-EM structures and biochemical analyses of the human mitoribosome, in complex with mitochondria-specific factors mediating mitoribosome recycling, RRFmt and EF-G2mt, offer insight into mechanisms of mitoribosome recycling and resistance to antibiotic fusidic acid.

    • Ravi Kiran Koripella
    • , Ayush Deep
    •  & Rajendra K. Agrawal
  • Article
    | Open Access

    Mitochondrial ribosomes (mitoribosomes) are characterized by a distinct architecture and thus biogenesis pathway. Here, cryo-EM structures of mitoribosome large subunit assembly intermediates elucidate final steps of 16 S rRNA folding, methylation and peptidyl transferase centre (PTC) completion, as well as functions of several mitoribosome assembly factors.

    • Caillan Crowe-McAuliffe
    • , Victoriia Murina
    •  & Daniel N. Wilson
  • Article
    | Open Access

    22G-RNAs are single-stranded antisense small RNAs that are expressed in C. elegans germline. Here the authors show that CSR-1 dependent 22G-RNAs are produced in the cytosol on mRNAs actively engaged in translation and that codon usage of an mRNA regulates the biogenesis of CSR-1 dependent 22G-RNAs.

    • Meetali Singh
    • , Eric Cornes
    •  & Germano Cecere
  • Article
    | Open Access

    The activity of translation initiation factor eIF2B is known to be modulated through stress-responsive phosphorylation of its substrate eIF2. Here, the authors uncover the regulation of eIF2B by the binding of sugar phosphates, suggesting a link between nutrient status and the rate of protein synthesis.

    • Qi Hao
    • , Jin-Mi Heo
    •  & Carmela Sidrauski
  • Article
    | Open Access

    Macrolide antibiotics inhibit bacterial translation in a context-specific manner, arresting ribosomes at defined sites within mRNAs and selectively inhibiting synthesis of only a subset of cellular proteins. Here the authors provide a structural basis for the context-specific activity of macrolides on the eukaryotic ribosome.

    • Maxim S. Svetlov
    • , Timm O. Koller
    •  & Alexander S. Mankin