The mechanism of ribosome recycling in eukaryotes

Pisarev, Andrey V.; Skabkin, Maxim A.; Pisareva, Vera P.; Hellen, Christopher U.T.; Pestova, Tatyana V.

doi:10.1007/978-3-7091-0215-2_14

Cited by 5 publications

(13 citation statements)

References 97 publications

(130 reference statements)

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“…Ski7 tethers the Ski complex to the cytoplasmic RNA exosome complex and thereby mediates mRNA degradation (Araki et al, 2001;Kowalinski et al, 2016;van Hoof et al, 2000). Hbs1 instead delivers Dom34 to stalled ribosomes, which allows Dom34 to recycle the ribosomal subunits for subsequent rounds of translation (Becker et al, 2011;Pisareva et al, 2011;Shoemaker et al, 2010). We further showed that this alternative splicing of SKI7/HBS1 is conserved in animals, fungi, and plants (Marshall et al, 2018;Marshall et al, 2013).…”

Section: Introductionmentioning

confidence: 74%

Origin, conservation, and loss of alternative splicing events that diversify the proteome in Saccharomycotina budding yeasts

Hurtig

Kim

Orlando-Coronel

et al. 2020

RNA

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Many eukaryotes use RNA processing, including alternative splicing, to express multiple gene products from the same gene. The budding yeast Saccharomyces cerevisiae has been successfully used to study the mechanism of splicing and the splicing machinery, but alternative splicing in yeast is relatively rare and has not been extensively studied. Alternative splicing of SKI7/HBS1 is widely conserved, but yeast and a few other eukaryotes have replaced this one alternatively spliced gene with a pair of duplicated, unspliced genes as part of a whole genome doubling (WGD). We show that other examples of alternative splicing known to have functional consequences are widely conserved within Saccharomycotina. A common mechanism by which alternative splicing has disappeared is by replacement of an alternatively spliced gene with duplicate unspliced genes. This loss of alternative splicing does not always take place soon after duplication, but can take place after sufficient time has elapsed for speciation. Saccharomycetaceae that diverged before WGD use alternative splicing more frequently than S. cerevisiae, suggesting that WGD is a major reason for infrequent alternative splicing in yeast. We anticipate that WGDs in other lineages may have had the same effect. Having observed that two functionally distinct splice-isoforms are often replaced by duplicated genes allowed us to reverse the reasoning. We thereby identify several splice isoforms that are likely to produce two functionally distinct proteins because we find them replaced by duplicated genes in related species. We also identify some alternative splicing events that are not conserved in closely related species and unlikely to produce functionally distinct proteins.

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Section: Introductionmentioning

confidence: 74%

Origin, conservation, and loss of alternative splicing events that diversify the proteome in Saccharomycotina budding yeasts

Hurtig

Kim

Orlando-Coronel

et al. 2020

RNA

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“…For an ATG classifier, these variables designated the ten nucleotides that preceded the codon, and ten that followed it. This range was chosen as studies suggest that alterations of bases in some of these positions are highly impactful, and may define whether a flanked codon is an "optimal, strong, [or] moderate" translation initiation site [13][14][15][16][17][18][19][20].…”

Section: Random Forest Classifiersmentioning

confidence: 99%

“…The performance of TITER may also be a result of the large number of features that this machine learning model incorporated. Although contemporary research suggests a few bases that flank a codon greatly influence translation initiation from the site [13][14][15][16][17][18][19][20], TITER analyzes a total of two hundred bases that flank each codon. Compared to our approach of analyzing ten preceding and proceeding nucleotides, TITER may implement up to 180*5 = 900 additional features.…”

Section: Analysis Of the Titer Neural Network As A Benchmarkmentioning

confidence: 99%

“…Ten sequence repeats may be adequate to capture the repeat expansion effect on translation initiation from upstream codons as well as codons within the repeat expansion itself because ten nucleotide sequence repeats are at minimum thirty bases long, and the integrated model only uses the ten bases that flank each side of a codon for analysis. Nucleotides within this range have been shown to strongly impact translation initiation [13][14][15][16][17][18][19][20].…”

Section: Model Selection and Integration Into Softwarementioning

confidence: 99%

“…The predictive models described in our investigations have 85.00-87.79% accuracy that exceeds that of TITER. Our models reduce the feature selection to capture the effect of ten critical nucleotides that flank both sides of a putative translation initiation codon since a number of studies have demonstrated a strong impact of nucleotides within this range on translation initiation [13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Machine learning predicts translation initiation sites in neurologic diseases with expanded repeats

Ghadge

et al. 2021

Preprint

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A number of neurologic diseases, including a form of amyotrophic lateral sclerosis and others associated with expanded nucleotide repeats have an unconventional form of translation called repeat-associated non-AUG (RAN) translation. Repeat protein products accumulate and are hypothesized to contribute to disease pathogenesis. It has been speculated that the repeat regions in the RNA fold into secondary structures in a length-dependent manner, promoting RAN translation. Additionally, nucleotides that flank the repeat region, especially ones closest to the initiation site, are believed to enhance translation initiation. Recently, a machine learning model based on a large number of flanking nucleotides has been proposed for identifying translation initiation sites. However, most likely due to its extensive feature selection and limited training data, the model has diminished predictive power. Here, we overcome this limitation and increase prediction accuracy by a) capturing the effect of nucleotides most critical for translation initiation via feature reduction, b) implementing an alternative machine learning algorithm better suited for limited data, c) building comprehensive and balanced training data (via sampling without replacement) that includes previously unavailable sequences, and, d) splitting ATG and near-cognate translation initiation codon data to train two separate models. We also design a supplementary scoring system to provide an additional prognostic assessment of model predictions. The resultant models have high performance, with 85.00-87.79% accuracy exceeding that of the previously published model by >18%. The models presented here are then used to identify translation initiation sites in genes associated with a number of neurologic repeat expansion disorders. The results confirm a number of experimentally discovered sites of translation initiation upstream of the expanded repeats and predict many sites that are not yet established.

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pSNAP: Proteome-wide analysis of elongating nascent polypeptide chains

Uchiyama

Roy

Wang

et al. 2021

Preprint

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Cellular global translation is often measured using ribosome profiling or quantitative mass spectrometry, but these methods do not provide direct information at the level of elongating nascent polypeptide chains (NPCs) and associated co-translational events. Here we describe pSNAP, a method for proteome-wide profiling of NPCs by affinity enrichment of puromycin- and stable isotope-labeled polypeptides. pSNAP does not require ribosome purification and/or chemical reaction, and captures bona fide NPCs that characteristically exhibit protein N-terminus-biased positions. We applied pSNAP to evaluate the effect of silmitasertib, a potential molecular therapy for cancer and COVID-19 patients, and revealed acute translational repression through casein kinase II and mTOR pathways. We also characterized modifications on NPCs and demonstrated that the combination of different types of modifications, such as acetylation and phosphorylation in the N-terminal region of histone H1.5, can modulate interactions with ribosome-associated factors. Thus, pSNAP provides a framework for dissecting co-translational regulations on a proteome-wide scale.

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The mechanism of ribosome recycling in eukaryotes

Cited by 5 publications

References 97 publications

Origin, conservation, and loss of alternative splicing events that diversify the proteome in Saccharomycotina budding yeasts

Origin, conservation, and loss of alternative splicing events that diversify the proteome in Saccharomycotina budding yeasts

Machine learning predicts translation initiation sites in neurologic diseases with expanded repeats

pSNAP: Proteome-wide analysis of elongating nascent polypeptide chains

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