Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Recent structural studies on Dom34/aPelota and Hbs1/aEF1?: important factors for solving general problems of ribosomal stall in translation.

ABSTRACT: In the translation process, translating ribosomes usually move on an mRNA until they reach the stop codon. However, when ribosomes translate an aberrant mRNA, they stall. Then, ribosomes are rescued from the aberrant mRNA, and the aberrant mRNA is subsequently degraded. In eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation. In archaea, aPelota and aEF1?, homologous to Pelota and Hbs1, respectively, are considered to be involved in that process. In recent years, great progress has been made in determining structures of Dom34/aPelota and Hbs1/aEF1?. In this review, we focus on the functional roles of Dom34/aPelota and Hbs1/aEF1? in ribosome rescue, based on recent structural studies of them. We will also present questions to be answered by future work.

SUBMITTER: Kobayashi K

PROVIDER: S-EPMC4629679 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Recent structural studies on Dom34/aPelota and Hbs1/aEF1α: important factors for solving general problems of ribosomal stall in translation.

Kobayashi Kan K Ishitani Ryuichiro R Nureki Osamu O

Biophysics (Nagoya-shi, Japan) 20130907

In the translation process, translating ribosomes usually move on an mRNA until they reach the stop codon. However, when ribosomes translate an aberrant mRNA, they stall. Then, ribosomes are rescued from the aberrant mRNA, and the aberrant mRNA is subsequently degraded. In eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation. In archaea, aPelota and aEF1α, homologous to Pelota and Hbs1, respectively, are considered to be invo ...[more]

PMID: 27493551

Similar Datasets

Structural insights into ribosomal rescue by Dom34 and Hbs1 at near-atomic resolution.

Project description:The surveillance of mRNA translation is imperative for homeostasis. Monitoring the integrity of the message is essential, as the translation of aberrant mRNAs leads to stalling of the translational machinery. During ribosomal rescue, arrested ribosomes are specifically recognized by the conserved eukaryotic proteins Dom34 and Hbs1, to initiate their recycling. Here we solve the structure of Dom34 and Hbs1 bound to a yeast ribosome programmed with a nonstop mRNA at 3.3?Å resolution using cryo-electron microscopy. The structure shows that Domain N of Dom34 is inserted into the upstream mRNA-binding groove via direct stacking interactions with conserved nucleotides of 18S rRNA. It senses the absence of mRNA at the A-site and part of the mRNA entry channel by direct competition. Thus, our analysis establishes the structural foundation for the recognition of aberrantly stalled 80S ribosomes by the Dom34·Hbs1·GTP complex during Dom34-mediated mRNA surveillance pathways.

| S-EPMC5187420 | biostudies-literature

Dom34-Hbs1 mediated dissociation of inactive 80S ribosomes promotes restart of translation after stress.

Project description:Following translation termination, ribosomal subunits dissociate to become available for subsequent rounds of protein synthesis. In many translation-inhibiting stress conditions, e.g. glucose starvation in yeast, free ribosomal subunits reassociate to form a large pool of non-translating 80S ribosomes stabilized by the 'clamping' Stm1 factor. The subunits of these inactive ribosomes need to be mobilized for translation restart upon stress relief. The Dom34-Hbs1 complex, together with the Rli1 NTPase (also known as ABCE1), have been shown to split ribosomes stuck on mRNAs in the context of RNA quality control mechanisms. Here, using in vitro and in vivo methods, we report a new role for the Dom34-Hbs1 complex and Rli1 in dissociating inactive ribosomes, thereby facilitating translation restart in yeast recovering from glucose starvation stress. Interestingly, we found that this new role is not restricted to stress conditions, indicating that in growing yeast there is a dynamic pool of inactive ribosomes that needs to be split by Dom34-Hbs1 and Rli1 to participate in protein synthesis. We propose that this provides a new level of translation regulation.

| S-EPMC3989619 | biostudies-literature

Dom34 Links Translation to Protein O-mannosylation.

Project description:In eukaryotes, Dom34 upregulates translation by securing levels of activatable ribosomal subunits. We found that in the yeast Saccharomyces cerevisiae and the human fungal pathogen Candida albicans, Dom34 interacts genetically with Pmt1, a major isoform of protein O-mannosyltransferase. In C. albicans, lack of Dom34 exacerbated defective phenotypes of pmt1 mutants, while they were ameliorated by Dom34 overproduction that enhanced Pmt1 protein but not PMT1 transcript levels. Translational effects of Dom34 required the 5'-UTR of the PMT1 transcript, which bound recombinant Dom34 directly at a CA/AC-rich sequence and regulated in vitro translation. Polysomal profiling revealed that Dom34 stimulates general translation moderately, but that it is especially required for translation of transcripts encoding Pmt isoforms 1, 4 and 6. Because defective protein N- or O-glycosylation upregulates transcription of PMT genes, it appears that Dom34-mediated specific translational upregulation of the PMT transcripts optimizes cellular responses to glycostress. Its translational function as an RNA binding protein acting at the 5'-UTR of specific transcripts adds another facet to the known ribosome-releasing functions of Dom34 at the 3'-UTR of transcripts.

| S-EPMC5074521 | biostudies-literature

Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay.

Project description:No-go decay (NGD) is one of several messenger RNA (mRNA) surveillance systems dedicated to the removal of defective mRNAs from the available pool. Two interacting factors, Dom34 and Hbs1, are genetically implicated in NGD in yeast. Using a reconstituted yeast translation system, we show that Dom34:Hbs1 interacts with the ribosome to promote subunit dissociation and peptidyl-tRNA drop-off. Our data further indicate that these recycling activities are shared by the homologous translation termination factor complex eRF1:eRF3, suggesting a common ancestral function. Because Dom34:Hbs1 activity exhibits no dependence on either peptide length or A-site codon identity, we propose that this quality-control system functions broadly to recycle ribosomes throughout the translation cycle whenever stalls occur.

| S-EPMC4022135 | biostudies-other

Internal ribosomal entry site-mediated translation is important for rhythmic PERIOD1 expression.

Project description:The mouse PERIOD1 (mPER1) plays an important role in the maintenance of circadian rhythm. Translation of mPer1 is directed by both a cap-dependent process and cap-independent translation mediated by an internal ribosomal entry site (IRES) in the 5' untranslated region (UTR). Here, we compared mPer1 IRES activity with other cellular IRESs. We also found critical region in mPer1 5'UTR for heterogeneous nuclear ribonucleoprotein Q (HNRNPQ) binding. Deletion of HNRNPQ binding region markedly decreased IRES activity and disrupted rhythmicity. A mathematical model also suggests that rhythmic IRES-dependent translation is a key process in mPER1 oscillation. The IRES-mediated translation of mPer1 will help define the post-transcriptional regulation of the core clock genes.

| S-EPMC3360671 | biostudies-literature

Solving Math Problems Approximately: A Developmental Perspective.

Project description:Although solving arithmetic problems approximately is an important skill in everyday life, little is known about the development of this skill. Past research has shown that when children are asked to solve multi-digit multiplication problems approximately, they provide estimates that are often very far from the exact answer. This is unfortunate as computation estimation is needed in many circumstances in daily life. The present study examined 4th graders, 6th graders and adults' ability to estimate the results of arithmetic problems relative to a reference number. A developmental pattern was observed in accuracy, speed and strategy use. With age there was a general increase in speed, and an increase in accuracy mainly for trials in which the reference number was close to the exact answer. The children tended to use the sense of magnitude strategy, which does not involve any calculation but relies mainly on an intuitive coarse sense of magnitude, while the adults used the approximated calculation strategy which involves rounding and multiplication procedures, and relies to a greater extent on calculation skills and working memory resources. Importantly, the children were less accurate than the adults, but were well above chance level. In all age groups performance was enhanced when the reference number was smaller (vs. larger) than the exact answer and when it was far (vs. close) from it, suggesting the involvement of an approximate number system. The results suggest the existence of an intuitive sense of magnitude for the results of arithmetic problems that might help children and even adults with difficulties in math. The present findings are discussed in the context of past research reporting poor estimation skills among children, and the conditions that might allow using children estimation skills in an effective manner.

| S-EPMC4865172 | biostudies-literature

Solving search problems by strongly simulating quantum circuits.

Project description:Simulating quantum circuits using classical computers lets us analyse the inner workings of quantum algorithms. The most complete type of simulation, strong simulation, is believed to be generally inefficient. Nevertheless, several efficient strong simulation techniques are known for restricted families of quantum circuits and we develop an additional technique in this article. Further, we show that strong simulation algorithms perform another fundamental task: solving search problems. Efficient strong simulation techniques allow solutions to a class of search problems to be counted and found efficiently. This enhances the utility of strong simulation methods, known or yet to be discovered, and extends the class of search problems known to be efficiently simulable. Relating strong simulation to search problems also bounds the computational power of efficiently strongly simulable circuits; if they could solve all problems in P this would imply that all problems in NP and #P could be solved in polynomial time.

| S-EPMC3565169 | biostudies-other

Young children selectively seek help when solving problems.

Project description:There is strong evidence that children show selectivity in their reliance on others as sources of information, but the findings to date have largely been limited to contexts that involve factual information. The current experiments were designed to determine whether children might also show selectivity in their choice of sources within a problem-solving context. Children in two age groups (20-24 months and 30-36 months, total N=60) were presented with a series of conceptually difficult problem-solving tasks and were given an opportunity to interact with adult experimenters who were depicted as either good helpers or bad helpers. Participants in both age groups preferred to seek help from the good helpers. The findings suggest that even young children evaluate others with reference to their potential to provide help and use this information to guide their behavioral choices.

| S-EPMC3661754 | biostudies-literature

Solving the problems of gas leakage at laparoscopy.

Project description:Gas leakage during minimally invasive surgery is an aerosolization hazard. Sensitive optical and thermographic imaging can demonstrate and differentiate between mechanistic categories, enabling engineering solutions to fortify surgical care against pollutants and pathogens affecting operating room teams. Areas for improvement.

| S-EPMC7461047 | biostudies-literature

Solving molecular docking problems with multi-objective metaheuristics.

Project description:Molecular docking is a hard optimization problem that has been tackled in the past with metaheuristics, demonstrating new and challenging results when looking for one objective: the minimum binding energy. However, only a few papers can be found in the literature that deal with this problem by means of a multi-objective approach, and no experimental comparisons have been made in order to clarify which of them has the best overall performance. In this paper, we use and compare, for the first time, a set of representative multi-objective optimization algorithms applied to solve complex molecular docking problems. The approach followed is focused on optimizing the intermolecular and intramolecular energies as two main objectives to minimize. Specifically, these algorithms are: two variants of the non-dominated sorting genetic algorithm II (NSGA-II), speed modulation multi-objective particle swarm optimization (SMPSO), third evolution step of generalized differential evolution (GDE3), multi-objective evolutionary algorithm based on decomposition (MOEA/D) and S-metric evolutionary multi-objective optimization (SMS-EMOA). We assess the performance of the algorithms by applying quality indicators intended to measure convergence and the diversity of the generated Pareto front approximations. We carry out a comparison with another reference mono-objective algorithm in the problem domain (Lamarckian genetic algorithm (LGA) provided by the AutoDock tool). Furthermore, the ligand binding site and molecular interactions of computed solutions are analyzed, showing promising results for the multi-objective approaches. In addition, a case study of application for aeroplysinin-1 is performed, showing the effectiveness of our multi-objective approach in drug discovery.

| S-EPMC6272647 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data