Translation

  • Article
    | Open Access

    Nonsense-mediated mRNA decay (NMD) was thought to ensue when ribosomes fail to terminate translation properly. However, the authors observe similar ribosome occupancy at stop codons of NMD sensitive and insensitive mRNAs, showing that human NMD is not activated by stable ribosome stalling as previously suggested.

    • Evangelos D. Karousis
    • , Lukas-Adrian Gurzeler
    •  & Oliver Mühlemann
  • Article
    | Open Access

    Rescue of ribosomes stalled on non-stop mRNA is essential for cell viability, and several rescue systems to resolve stalling exist in bacteria. Here, the authors use rapid kinetics and cryo-EM to reveal the pathway and selectivity mechanism of ArfB-mediated ribosome rescue.

    • Kai-Hsin Chan
    • , Valentyn Petrychenko
    •  & Marina V. Rodnina
  • Article
    | Open Access

    The relative abundance of specific tRNA can impact protein production rate, folding, and messenger RNA stability. Here the authors describe QuantM-tRNA seq — a method to monitor tRNA abundance and sequence variants — and uncover distinctions in isodecoder expression between tissues that are independent of the anticodon pool of each tRNA family.

    • Otis Pinkard
    • , Sean McFarland
    •  & Jeff Coller
  • Article
    | Open Access

    Antibiotics targeting protein translation interact in hard-to-predict ways. Here, Kavčič et al. interpret these interactions in terms of translation bottlenecks, the kinetics of drug uptake and target binding, bacterial growth laws, and a model of queued traffic progression.

    • Bor Kavčič
    • , Gašper Tkačik
    •  & Tobias Bollenbach
  • Article
    | Open Access

    Translation within mitochondria is carried out by specialized mitoribosomes and translational factors. Here the authors describe cryo-EM structures of the human mitochondrial translation elongation factor G1 in complex with human mitoribosomes, revealing distinct mechanism that include conformational changes at the polypeptide exit tunnel.

    • Ravi Kiran Koripella
    • , Manjuli R. Sharma
    •  & Rajendra K. Agrawal
  • Article
    | Open Access

    As assembling 60S subunits transit from the nucleolus to the nucleoplasm, they undergo significant changes in protein composition and structure. Here, the authors provide a structural view of interconnected events during the middle steps of assembly that include the maturation of the central protuberance, the peptidyltransferase center and the nascent polypeptide exit tunnel.

    • Jelena Micic
    • , Yu Li
    •  & John L. Woolford Jr.
  • Article
    | Open Access

    Ribosome biogenesis in eukaryotes is a complex process that involves more than 200 protein factors. Here the authors present a structural analysis of a collection of human pre-60S structures sampled through a nuclear export adaptor NMD3, representing structural snapshots of pre-60S particles immediately before and after passing through nuclear pore complex.

    • Xiaomeng Liang
    • , Mei-Qing Zuo
    •  & Ning Gao
  • Article
    | Open Access

    Phosphorylation of eIF4E binding proteins (4E-BPs) controls their folding and regulates cap-dependent translation. Here, the authors show that phosphorylation of the C-terminal disordered region stabilizes the non-cooperatively folded 4E-BP domain to an eIF4E binding-incompatible state to control translation.

    • Jennifer E. Dawson
    • , Alaji Bah
    •  & Julie D. Forman-Kay
  • Article
    | Open Access

    Programmed ribosomal frameshifting—the slippage of the ribosome to an alternative frame — is critical for viral replication and cellular processes. Here the authors present an approach that can assess the frameshifting potential of a sequence and elucidate the rules governing ribosomal frameshifting.

    • Martin Mikl
    • , Yitzhak Pilpel
    •  & Eran Segal
  • Article
    | Open Access

    Translation within mitochondria relies upon specialized mitoribosomes and initiation factors. Here the authors use Cryo-EM and single molecule approaches to describe the early steps leading to translation initiation in human mitochondria, and the roles of mitochondria-specific ribosomal proteins and initiation factors mtIF2 and mtIF3.

    • Anas Khawaja
    • , Yuzuru Itoh
    •  & Joanna Rorbach
  • Article
    | Open Access

    Ribosomes of all organisms have retained 5S rRNA as an autonomous rRNA species. Here the authors engineer a bacterial strain with ribosomes that do not have free 5S rRNA, and carry structural analyses that suggest the evolutionary preservation of 5S rRNA as an independent molecule is based on its role in the dynamic process of ribosome biogenesis.

    • Shijie Huang
    • , Nikolay A. Aleksashin
    •  & Alexander S. Mankin
  • Article
    | Open Access

    The DIS3L2 exonuclease degrades aberrant 7SL RNAs tagged by an oligouridine 3′-tail. Here the authors analyze DIS3L2 knockout mouse embryonic stem cells and suggest that DIS3L2-mediated quality control of 7SL RNA is important for ER-mediated translation and calcium ion homeostasis.

    • Mehdi Pirouz
    • , Chih-Hao Wang
    •  & Richard I. Gregory
  • Article
    | Open Access

    Gene regulation and metabolism co-ordinate self-renewal and differentiation of neural precursors (NPCs) in the developing brain. Here the authors show that methylglyoxal, a glycolytic intermediate metabolite, promotes GADPH-dependent translational repression of Notch1, thereby promoting NPC differentiation.

    • Deivid Carvalho Rodrigues
    • , Emily M. Harvey
    •  & Guang Yang
  • Article
    | Open Access

    Ribosome engineering is an emerging powerful approach for synthetic protein synthesis. Here the authors invert the Ribo-T system, using the engineered ribosome to translate the proteome while the native ribosome translates specific mRNA.

    • Nikolay A. Aleksashin
    • , Teresa Szal
    •  & Alexander S. Mankin
  • Article
    | Open Access

    Upon transition to stationary phase or upon stress, bacteria limit protein synthesis through small inhibitory proteins that bind the ribosome. Here the authors decipher the interaction mode of the bacterial ribosome silencing factor (RsfS) at atomic details to provide an in depth view of how it shutdowns ribosomes.

    • Iskander Khusainov
    • , Bulat Fatkhullin
    •  & Marat Yusupov
  • Article
    | Open Access

    Directed evolution of the ribosome is challenging because the requirement of cell viability limits the mutations that can be made. Here the authors develop a platform for in vitro ribosome synthesis and evolution (RISE) to overcome these constraints.

    • Michael J. Hammerling
    • , Brian R. Fritz
    •  & Michael C. Jewett
  • Article
    | Open Access

    Bilaterian mitochondria-encoded tRNA genes accumulate mutations at higher rates than their cytoplasmic tRNA counterparts, resulting in idiosyncratic structures. Here the authors suggest an evolutionary basis for the observed mutational freedom of mitochondrial (mt) tRNAs and reveal the associated co-adaptive structural and functional changes in mt aminoacyl-tRNA synthetases.

    • Bernhard Kuhle
    • , Joseph Chihade
    •  & Paul Schimmel
  • Article
    | Open Access

    The ErbB3 receptor binding protein Ebp1 binds to ribosomes and is linked to translational control. Here, the authors present the cryo-EM structure of human Ebp1 bound to a non-translating 80S ribosome and find that Ebp1 blocks the tunnel exit and recruits the rRNA expansion segment ES27L to the tunnel exit.

    • Klemens Wild
    • , Milan Aleksić
    •  & Irmgard Sinning
  • Article
    | Open Access

    Several factors contribute to the efficiency of protein expression. Here the authors show that the identity of amino acids encoded by codons at position 3–5 significantly impact translation efficiency and protein expression levels.

    • Manasvi Verma
    • , Junhong Choi
    •  & Sergej Djuranovic
  • Article
    | Open Access

    E. coli and human tRNAs contain 3-(3-amino-3-carboxypropyl)uridine (acp3U) modification. Here the authors identify E. coli TapT and human DTWD1/2 as tRNA aminocarboxypropyltransferases responsible for acp3U formation. Inhibition of acp3U modification results in genome instability in heat-stressed E. coli and growth defects in human cells.

    • Mayuko Takakura
    • , Kensuke Ishiguro
    •  & Tsutomu Suzuki
  • Article
    | Open Access

    In bacteria, the conserved trans-translation system serves as the primary pathway of ribosome rescue, but many species can also use alternative rescue pathways. Here the authors report that in B. subtilis, the rescue factor BrfA binds to non-stop stalled ribosomes, recruits RF2 but not RF1, and induces transition of the ribosome into an open active conformation.

    • Naomi Shimokawa-Chiba
    • , Claudia Müller
    •  & Shinobu Chiba
  • Article
    | Open Access

    Programmed ribosomal frameshifting (PRF) is an alternative translation strategy that causes controlled slippage of the ribosome along the mRNA, changing the sequence of the synthesized protein. Here the authors provide a thermodynamic framework that explains how mRNA sequence determines the efficiency of frameshifting.

    • Lars V. Bock
    • , Neva Caliskan
    •  & Helmut Grubmüller
  • Article
    | Open Access

    Archaea and bacteria often have gene pairs with overlapping stop and start codons, suggesting translational coupling. Here, Huber et al. analyse overlapping gene pairs from 720 genomes, and validate translational coupling via termination-reinitiation for 14 gene pairs in Haloferax volcanii and Escherichia coli.

    • Madeleine Huber
    • , Guilhem Faure
    •  & Jörg Soppa
  • Article
    | Open Access

    Pituitary POMC secreting cells achieve high hormone expression levels after birth but the mechanism for this regulation is unclear. Here, the authors show that this process is driven cell autonomously by the differentiation factor Tpit that activates the bZIP transcription factors Creb3l2 and XBP1 to enhance translation and secretory capacities.

    • Konstantin Khetchoumian
    • , Aurélio Balsalobre
    •  & Jacques Drouin
  • Article
    | Open Access

    The biosynthesis of N6-threonylcarbamoylated adenosine 37 in tRNA (t6A) involves the YRDC enzyme and the KEOPS complex. Here, the authors report mutations in YRDC and the KEOPS component GON7 in Galloway-Mowat syndrome and determine the crystal structure of a GON7-containg subcomplex that suggests a role in KEOPS complex stability.

    • Christelle Arrondel
    • , Sophia Missoury
    •  & Géraldine Mollet
  • Article
    | Open Access

    Ribo-T is a tethered ribosome complex capable of orthogonal ribosome-mRNA functionality, but has low activity. Here the authors evolve new tether designs that support faster growth and increased protein expression.

    • Erik D. Carlson
    • , Anne E. d’Aquino
    •  & Michael C. Jewett
  • Article
    | Open Access

    MazF endoribonucleases are thought to arrest growth of Mycobacterium tuberculosis by global translation inhibition. Here, Barth et al. show that MazF-mt9 cleaves a specific tRNA, leading to ribosome stalling at AAA codons and thus selective mRNA degradation and changes in transcriptome and proteome.

    • Valdir C. Barth
    • , Ju-Mei Zeng
    •  & Nancy A. Woychik
  • Article
    | Open Access

    Adenovirus Virus-Associated (VA) noncoding RNAs interfere with the host system by mimicking double stranded RNAs. Here, the authors report a 2.7 Å crystal structure of VA-I RNA providing an understanding of its function.

    • Iris V. Hood
    • , Jackson M. Gordon
    •  & Jinwei Zhang
  • Article
    | Open Access

    5-carboxymethoxyuridine (cmo5U) is one of the RNA modifications found in bacterial tRNA anticodons. Here the authors show that the first step of cmo5U biosynthesis from uridine is mediated by either one of two parallel factors, TrhP or TrhO, and that cmo5U modification is required for efficient translation.

    • Yusuke Sakai
    • , Satoshi Kimura
    •  & Tsutomu Suzuki
  • Article
    | Open Access

    During stress, protein synthesis is inhibited through phosphorylation of the initiation factor eIF2 on its alpha subunit and its interaction with eIF2B. Here the authors describe a structure of the yeast eIF2B in complex with its substrate - the GDP-bound phosphorylated eIF2, providing insights into how phosphorylation results in a tighter interaction with eIF2B.

    • Yuliya Gordiyenko
    • , José Luis Llácer
    •  & V. Ramakrishnan
  • Article
    | Open Access

    Metal ions play essential roles in myriads of biological processes, from catalytic co-factors to supporting protein and nucleic acid structures. Here the authors use long-wavelength X-ray diffraction to locate hundreds of potassium ions taking part in the formation of rRNA tertiary structure, mediating rRNA–protein interactions and supporting ribosomal protein structures and function.

    • Alexey Rozov
    • , Iskander Khusainov
    •  & Gulnara Yusupova
  • Article
    | Open Access

    The nuclear pore complex (NPC) is known to regulate p53 signaling and this has mainly been linked to peripheral NPC subunits. Here the authors show that Nup155 from the NPC inner ring regulates the p53 pathway by controlling p21 translation while also being a target of p53-mediated repression.

    • Kerstin Holzer
    • , Alessandro Ori
    •  & Stephan Singer
  • Article
    | Open Access

    During the integrated stress response, translation is modulated through the phosphorylation of translation initiation factor eIF2 and the formation of a complex with eIF2B. Here the authors present structures of the eIF2:eIF2B complex with and without phosphorylation, shedding light on how eIF2 phosphorylation regulates translation.

    • Tomas Adomavicius
    • , Margherita Guaita
    •  & Graham D. Pavitt
  • Article
    | Open Access

    Genes encoding protein complex subunits are often dispersed in the genome of eukaryotes, raising the question how these protein complexes assemble. Here, the authors provide evidence that mammalian nuclear transcription complexes are formed co-translationally to ensure specific and functional interactions.

    • Ivanka Kamenova
    • , Pooja Mukherjee
    •  & László Tora
  • Article
    | Open Access

    The initiation of translation is a highly regulated process that contributes to specific gene expression programs. Here the authors find that, in vertebrate, threonyl-tRNA synthetase (TRS) can act as a scaffold for the initiation machinery to stimulate the translation of a specific set of mRNAs.

    • Seung Jae Jeong
    • , Shinhye Park
    •  & Sunghoon Kim
  • Article
    | Open Access

    In eukaryotes, ribosome biogenesis culminates in the cytoplasm with the maturation of the peptidyl transfer center (PTC). Here the authors describe several structures of intermediates in late nuclear and cytoplasmic maturation of the large ribosomal subunit that reveal the tightly-choreographed sequence of protein and RNA rearrangements that lead to the completion of the PTC.

    • Yi Zhou
    • , Sharmishtha Musalgaonkar
    •  & David W. Taylor
  • Article
    | Open Access

    The tethered ribosome system Ribo-T supports cell proliferation though at a reduced rate. Here the authors show this is due to slower ribosome assembly instead of reduced functionality.

    • Nikolay A. Aleksashin
    • , Margus Leppik
    •  & Alexander S. Mankin
  • Article
    | Open Access

    Viruses can encode genes that regulate the host's translational machinery to their advantage. Here, the authors show that viruses encode ribosomal proteins that can be incorporated into the host’s ribosome and may affect translation.

    • Carolina M. Mizuno
    • , Charlotte Guyomar
    •  & Mart Krupovic
  • Article
    | Open Access

    The antitermination factor RfaH adopts two functional states where its C-terminal domain is folded either as an α-helical hairpin or β-barrel. Here the authors employ solution state NMR measurements to show that the C-terminal domain transforms into the β-barrel only upon binding to the elongation complex and refolds back after dissociation.

    • Philipp Konrad Zuber
    • , Kristian Schweimer
    •  & Stefan H. Knauer
  • Article
    | Open Access

    Rix7 is a type II AAA-ATPase that is required for the assembly of the large ribosomal subunit. Here the authors present the 4.5 Å cryo-EM structure of the Rix7 homohexamer with a polypeptide fragment bound in its central channel and provide insights into the function of Rix7 as a molecular unfoldase.

    • Yu-Hua Lo
    • , Mack Sobhany
    •  & Robin E. Stanley