keyword
MENU ▼
Read by QxMD icon Read
search

ribosome stall

keyword
https://www.readbyqxmd.com/read/28757607/ubiquitination-of-stalled-ribosome-triggers-ribosome-associated-quality-control
#1
Yoshitaka Matsuo, Ken Ikeuchi, Yasushi Saeki, Shintaro Iwasaki, Christian Schmidt, Tsuyoshi Udagawa, Fumiya Sato, Hikaru Tsuchiya, Thomas Becker, Keiji Tanaka, Nicholas T Ingolia, Roland Beckmann, Toshifumi Inada
Translation arrest by polybasic sequences induces ribosome stalling, and the arrest product is degraded by the ribosome-mediated quality control (RQC) system. Here we report that ubiquitination of the 40S ribosomal protein uS10 by the E3 ubiquitin ligase Hel2 (or RQT1) is required for RQC. We identify a RQC-trigger (RQT) subcomplex composed of the RNA helicase-family protein Slh1/Rqt2, the ubiquitin-binding protein Cue3/Rqt3, and yKR023W/Rqt4 that is required for RQC. The defects in RQC of the RQT mutants correlate with sensitivity to anisomycin, which stalls ribosome at the rotated form...
July 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28751611/cat-tailing-as-a-fail-safe-mechanism-for-efficient-degradation-of-stalled-nascent-polypeptides
#2
Kamena K Kostova, Kelsey L Hickey, Beatriz A Osuna, Jeffrey A Hussmann, Adam Frost, David E Weinberg, Jonathan S Weissman
Ribosome stalling leads to recruitment of the ribosome quality control complex (RQC), which targets the partially synthesized polypeptide for proteasomal degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here we examined the role of CAT-tailing in nascent-chain degradation in budding yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines immediately proximal to the ribosome exit tunnel...
July 28, 2017: Science
https://www.readbyqxmd.com/read/28745585/maturation-of-selected-human-mitochondrial-trnas-requires-deadenylation
#3
Sarah F Pearce, Joanna Rorbach, Lindsey Van Haute, Aaron R D'Souza, Pedro Rebelo-Guiomar, Christopher A Powell, Ian Brierley, Andrew E Firth, Michal Minczuk
Human mitochondria contain a genome (mtDNA) that encodes essential subunits of the oxidative phosphorylation system. Expression of mtDNA entails multi-step maturation of precursor RNA. In other systems, the RNA life cycle involves surveillance mechanisms, however, the details of RNA quality control have not been extensively characterised in human mitochondria. Using a mitochondrial ribosome profiling and mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq) assay, we identify the poly(A)-specific exoribonuclease PDE12 as a major factor for the quality control of mitochondrial non-coding RNAs...
July 26, 2017: ELife
https://www.readbyqxmd.com/read/28741611/an-antimicrobial-peptide-that-inhibits-translation-by-trapping-release-factors-on-the-ribosome
#4
Tanja Florin, Cristina Maracci, Michael Graf, Prajwal Karki, Dorota Klepacki, Otto Berninghausen, Roland Beckmann, Nora Vázquez-Laslop, Daniel N Wilson, Marina V Rodnina, Alexander S Mankin
Many antibiotics stop bacterial growth by inhibiting different steps of protein synthesis. However, no specific inhibitors of translation termination are known. Proline-rich antimicrobial peptides, a component of the antibacterial defense system of multicellular organisms, interfere with bacterial growth by inhibiting translation. Here we show that Api137, a derivative of the insect-produced antimicrobial peptide apidaecin, arrests terminating ribosomes using a unique mechanism of action. Api137 binds to the Escherichia coli ribosome and traps release factor (RF) RF1 or RF2 subsequent to the release of the nascent polypeptide chain...
July 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28733601/anti-tubercular-activity-of-pyrazinamide-is-independent-of-trans-translation-and-rpsa
#5
Nicholas A Dillon, Nicholas D Peterson, Heather A Feaga, Kenneth C Keiler, Anthony D Baughn
Pyrazinamide (PZA) is a first line anti-tubercular drug for which the mechanism of action remains unresolved. Recently, it was proposed that the active form of PZA, pyrazinoic acid (POA), disrupts the ribosome rescue process of trans-translation in Mycobacterium tuberculosis. This model suggested that POA binds within the carboxy-terminal domain of ribosomal protein S1 (RpsA) and inhibits trans-translation leading to accumulation of stalled ribosomes. Here, we demonstrate that M. tuberculosis RpsA interacts with single stranded RNA, but not with POA...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718767/in-vitro-analysis-of-rqc-activities-provides-insights-into-the-mechanism-and-function-of-cat-tailing
#6
Beatriz A Osuna, Conor J Howard, Subheksha Kc, Adam Frost, David E Weinberg
Ribosomes can stall during translation due to defects in the mRNA template or translation machinery, leading to the production of incomplete proteins. The Ribosome-associated Quality control Complex (RQC) engages stalled ribosomes and targets nascent polypeptides for proteasomal degradation. However, how each RQC component contributes to this process remains unclear. Here we demonstrate that key RQC activities-Ltn1p-dependent ubiquitination and Rqc2p-mediated Carboxy-terminal Alanine and Threonine (CAT) tail elongation-can be recapitulated in vitro with a yeast cell-free system...
July 18, 2017: ELife
https://www.readbyqxmd.com/read/28715909/ribosomal-stalling-during-translation-providing-substrates-for-ribosome-associated-protein-quality-control
#7
Claudio A P Joazeiro
Cells of all organisms survey problems during translation elongation, which may happen as a consequence of mRNA aberrations, inefficient decoding, or other sources. In eukaryotes, ribosome-associated quality control (RQC) senses elongation-stalled ribosomes and promotes dissociation of ribosomal subunits. This so-called ribosomal rescue releases the mRNA for degradation and allows 40S subunits to be recycled for new rounds of translation. However, the nascent polypeptide chains remain linked to tRNA and associated with the rescued 60S subunits...
July 17, 2017: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/28705956/rapid-recovery-gene-downregulation-during-excess-light-stress-and-recovery-in-arabidopsis
#8
Peter Alexander Crisp, Diep Ganguly, Aaron B Smith, Kevin D Murray, Gonzalo M Estavillo, Iain R Searle, Ethan Ford, Ozren Bogdanović, Ryan Lister, Justin O Borevitz, Steven R Eichten, Barry J Pogson
Stress recovery may prove to be a promising approach to increase plant performance, and theoretically, mRNA instability may facilitate faster recovery. Transcriptome (RNA-seq, qPCR, sRNA-seq, PARE) and methylome profiling during repeated excess-light stress and recovery was performed at intervals as short as three minutes. We demonstrate that 87% of the stress-upregulated mRNAs analysed exhibit very rapid recovery. For instance, HSP101 abundance declined two-fold every 5.1 minutes. We term this phenomenon Rapid Recovery Gene Downregulation (RRGD), whereby mRNA abundance rapidly decreases promoting transcriptome resetting...
July 13, 2017: Plant Cell
https://www.readbyqxmd.com/read/28702280/dissecting-limiting-factors-of-the-protein-synthesis-using-recombinant-elements-pure-system
#9
Jun Li, Chi Zhang, Poyi Huang, Erkin Kuru, Eliot T C Forster-Benson, Taibo Li, George M Church
Reconstituted cell-free protein synthesis systems such as the Protein synthesis Using Recombinant Elements (PURE) system give high-throughput and controlled access to in vitro protein synthesis. Here we show that compared with the commercial S30 crude extract based RTS 100 E. coli HY system, the PURE system has less mRNA degradation and produces up to ∼6-fold full-length proteins. However the majority of polypeptides PURE produces are partially translated or inactive since the signal from firefly luciferase (Fluc) translated in PURE is only ∼2/3(rd) of that measured using the RTS 100 E...
2017: Translation
https://www.readbyqxmd.com/read/28630923/ribosome-rearrangements-at-the-onset-of-translational-bypassing
#10
Xabier Agirrezabala, Ekaterina Samatova, Mariia Klimova, Miguel Zamora, David Gil-Carton, Marina V Rodnina, Mikel Valle
Bypassing is a recoding event that leads to the translation of two distal open reading frames into a single polypeptide chain. We present the structure of a translating ribosome stalled at the bypassing take-off site of gene 60 of bacteriophage T4. The nascent peptide in the exit tunnel anchors the P-site peptidyl-tRNA(Gly) to the ribosome and locks an inactive conformation of the peptidyl transferase center (PTC). The mRNA forms a short dynamic hairpin in the decoding site. The ribosomal subunits adopt a rolling conformation in which the rotation of the small subunit around its long axis causes the opening of the A-site region...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28629612/structural-basis-for-ribosome-rescue-in-bacteria
#11
REVIEW
Paul Huter, Claudia Müller, Stefan Arenz, Bertrand Beckert, Daniel N Wilson
Ribosomes that translate mRNAs lacking stop codons become stalled at the 3' end of the mRNA. Recycling of these stalled ribosomes is essential for cell viability. In bacteria three ribosome rescue systems have been identified so far, with the most ubiquitous and best characterized being the trans-translation system mediated by transfer-messenger RNA (tmRNA) and small protein B (SmpB). The two additional rescue systems present in some bacteria employ alternative rescue factor (Arf) A and release factor (RF) 2 or ArfB...
June 16, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28588135/spatial-distribution-and-ribosome-binding-dynamics-of-ef-p-in-live-escherichia%C3%A2-coli
#12
Sonisilpa Mohapatra, Heejun Choi, Xueliang Ge, Suparna Sanyal, James C Weisshaar
In vitro assays find that ribosomes form peptide bonds to proline (Pro) residues more slowly than to other residues. Ribosome profiling shows that stalling at Pro-Pro-X triplets is especially severe but is largely alleviated in Escherichia coli by the action of elongation factor EF-P. EF-P and its eukaryotic/archaeal homolog IF5A enhance the peptidyl transfer step of elongation. Here, a superresolution fluorescence localization and tracking study of EF-P-mEos2 in live E. coli provides the first in vivo information about the spatial distribution and on-off binding kinetics of EF-P...
June 6, 2017: MBio
https://www.readbyqxmd.com/read/28582582/codon-usage-regulates-protein-structure-and-function-by-affecting-translation-elongation-speed-in-drosophila-cells
#13
Fangzhou Zhao, Chien-Hung Yu, Yi Liu
Codon usage biases are found in all eukaryotic and prokaryotic genomes and have been proposed to regulate different aspects of translation process. Codon optimality has been shown to regulate translation elongation speed in fungal systems, but its effect on translation elongation speed in animal systems is not clear. In this study, we used a Drosophila cell-free translation system to directly compare the velocity of mRNA translation elongation. Our results demonstrate that optimal synonymous codons speed up translation elongation while non-optimal codons slow down translation...
June 5, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28556777/the-force-sensing-peptide-vemp-employs-extreme-compaction-and-secondary-structure-formation-to-induce-ribosomal-stalling
#14
Ting Su, Jingdong Cheng, Daniel Sohmen, Rickard Hedman, Otto Berninghausen, Gunnar von Heijne, Daniel N Wilson, Roland Beckmann
Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 Å cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two α-helices connected by an α-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50-55 Å of the exit tunnel...
May 30, 2017: ELife
https://www.readbyqxmd.com/read/28549188/eif5a-facilitates-translation-termination-globally-and-promotes-the-elongation-of-many-non-polyproline-specific-tripeptide-sequences
#15
Vicent Pelechano, Paula Alepuz
eIF5A is an essential protein involved in protein synthesis, cell proliferation and animal development. High eIF5A expression is observed in many tumor types and has been linked to cancer metastasis. Recent studies have shown that eIF5A facilitates the translation elongation of stretches of consecutive prolines. Activated eIF5A binds to the empty E-site of stalled ribosomes, where it is thought to interact with the peptidyl-tRNA situated at the P-site. Here, we report a genome-wide analysis of ribosome stalling in Saccharomyces cerevisiae eIF5A depleted cells using 5Pseq...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28528489/the-ribosome-bound-quality-control-complex-from-aberrant-peptide-clearance-to-proteostasis-maintenance
#16
REVIEW
Quentin Defenouillère, Micheline Fromont-Racine
Proteostasis in eukaryotes is maintained by compartment-specific quality control pathways, which enable the refolding or the degradation of defective polypeptides to prevent the toxicity that may arise from their aggregation. Among these processes, translational protein quality control is performed by the Ribosome-bound Quality Control complex (RQC), which recognizes nascent peptides translated from aberrant mRNAs, polyubiquitylates these aberrant peptides, extracts them from the stalled 60S subunit and finally escorts them to the proteasome for degradation...
May 20, 2017: Current Genetics
https://www.readbyqxmd.com/read/28525745/conditional-switch-between-frameshifting-regimes-upon-translation-of-dnax-mrna
#17
Neva Caliskan, Ingo Wohlgemuth, Natalia Korniy, Michael Pearson, Frank Peske, Marina V Rodnina
Ribosome frameshifting during translation of bacterial dnaX can proceed via different routes, generating a variety of distinct polypeptides. Using kinetic experiments, we show that -1 frameshifting predominantly occurs during translocation of two tRNAs bound to the slippery sequence codons. This pathway depends on a stem-loop mRNA structure downstream of the slippery sequence and operates when aminoacyl-tRNAs are abundant. However, when aminoacyl-tRNAs are in short supply, the ribosome switches to an alternative frameshifting pathway that is independent of a stem-loop...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525744/ctf4-prevents-genome-rearrangements-by-suppressing-dna-double-strand-break-formation-and-its-end-resection-at-arrested-replication-forks
#18
Mariko Sasaki, Takehiko Kobayashi
Arrested replication forks lead to DNA double-strand breaks (DSBs), which are a major source of genome rearrangements. Yet DSB repair in the context of broken forks remains poorly understood. Here we demonstrate that DSBs that are formed at arrested forks in the budding yeast ribosomal RNA gene (rDNA) locus are normally repaired by pathways dependent on the Mre11-Rad50-Xrs2 complex but independent of HR. HR is also dispensable for DSB repair at stalled forks at tRNA genes. In contrast, in cells lacking the core replisome component Ctf4, DSBs are formed more frequently, and these DSBs undergo end resection and HR-mediated repair that is prone to rDNA hyper-amplification; this highlights Ctf4 as a key regulator of DSB end resection at arrested forks...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28522328/inhibiting-translation-one-protein-at-a-time
#19
Matthew D Disney
Historically, translational inhibitors have been confined to anti-bacterials that globally affect translation. Lintner et al. demonstrate that small molecules can specifically inhibit translation of a single disease-associated protein by stalling the ribosome's nascent chain [1], opening up a new therapeutic strategy for 'undruggable' proteins.
May 15, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28507157/translation-and-folding-of-single-proteins-in-real-time
#20
Florian Wruck, Alexandros Katranidis, Knud H Nierhaus, Georg Büldt, Martin Hegner
Protein biosynthesis is inherently coupled to cotranslational protein folding. Folding of the nascent chain already occurs during synthesis and is mediated by spatial constraints imposed by the ribosomal exit tunnel as well as self-interactions. The polypeptide's vectorial emergence from the ribosomal tunnel establishes the possible folding pathways leading to its native tertiary structure. How cotranslational protein folding and the rate of synthesis are linked to a protein's amino acid sequence is still not well defined...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
keyword
keyword
97983
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"