Receptor for activated C kinase 1 stimulates nascent polypeptide‐dependent translation arrest

Kuroha, Kazushige; Akamatsu, Mayuko; Dimitrova, Lyudmila; Ito, Takehiko; Kato, Yuki; Shirahige, Katsuhiko; Inada, Toshifumi

doi:10.1038/embor.2010.169

Cited by 160 publications

(224 citation statements)

References 25 publications

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“…These include the ubiquitin ligases Ltn1 and Hel2, the ribosome-associated scaffold protein Asc1, and most likely the other components of the RQC complex (Kuroha et al 2010;Brandman et al 2012). Ltn1 targets the polypeptide product upstream of the CGA codons, as well as the nascent polypeptide from a message lacking a stop codon (Wilson et al 2007;Bengtson and Joazeiro 2010).…”

Section: Discussionmentioning

confidence: 99%

“…ASC1 and HEL2 exacerbate the effects of internal, but not N-terminal, CGA codons Two other proteins, Asc1, the yeast homolog of RACK1, and Hel2, a putative E3 ubiquitin ligase, have been specifically implicated in translation through polybasic peptide sequences, since deletion of either ASC1 or HEL2 improves expression of sequences downstream from 12 amino acid polybasic repeats (Kuroha et al 2010;Brandman et al 2012). Since Ltn1 was also implicated in the inhibitory effects of polybasic peptide sequences (Wilson et al 2007;Dimitrova et al 2009;Bengtson and Joazeiro 2010;Brandman et al 2012), we investigated the effects of ASC1 and HEL2 on CGA-mediated translation inhibition.…”

Section: Protein Synthesis Is Discontinued At Cga Codon Repeatsmentioning

confidence: 99%

“…Similarly, in eukaryotes there are translational quality control systems that respond to any of the following features: the absence of a stop codon van Hoof et al 2002); the presence of an inhibitory mRNA structure that prevents continued elongation (Doma and Parker 2006); the presence of polybasic nascent-peptide sequences, which are thought to interact with the exit tunnel (Ito-Harashima et al 2007); or the presence of premature stop codons (Isken and Maquat 2007). In each of these cases, the problem is resolved by releasing the ribosome and by removal of the mRNA (Doma and Parker 2006;Isken and Maquat 2007;Kuroha et al 2010;Shoemaker and Green 2012), which, in at least some instances, is accompanied by endonucleolytic cleavage of the mRNA near the stalled ribosome (Doma and Parker 2006;Huntzinger et al 2008;Tsuboi et al 2012). In two examples in yeast, the nascent protein products are targeted for proteolytic degradation by either of two E3 ubiquitin ligases, Not4 or Ltn1 (also called Rkr1) (Wilson et al 2007;Dimitrova et al 2009;Bengtson and Joazeiro 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Two genes, ASC1 and HEL2, have been implicated in the cessation of translation at polybasic sites, since deletion of either one of these genes results in increased read through into the downstream sequences (Kuroha et al 2010;Brandman et al 2012). Asc1, the yeast homolog of human RACK1, is a stoichiometric component of the small subunit of the ribosome (Gerbasi et al 2004), that is implicated in numerous signaling events (Nilsson et al 2004), in recruitment of the mRNA binding protein Scp150 (Coyle et al 2009) and in P-body formation in response to hydroxyurea treatment (Tkach et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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Translation of CGA codon repeats in yeast involves quality control components and ribosomal protein L1

Letzring

Wolf

Brule

et al. 2013

RNA

108

145

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Translation of CGA codon repeats in the yeast Saccharomyces cerevisiae is inefficient, resulting in dose-dependent reduction in expression and in production of an mRNA cleavage product, indicative of a stalled ribosome. Here, we use genetics and translation inhibitors to understand how ribosomes respond to CGA repeats. We find that CGA codon repeats result in a truncated polypeptide that is targeted for degradation by Ltn1, an E3 ubiquitin ligase involved in nonstop decay, although deletion of LTN1 does not improve expression downstream from CGA repeats. Expression downstream from CGA codons at residue 318, but not at residue 4, is improved by deletion of either ASC1 or HEL2, previously implicated in inhibition of translation by polybasic sequences. Thus, translation of CGA repeats likely causes ribosomes to stall and exploits known quality control systems. Expression downstream from CGA repeats at amino acid 4 is improved by paromomycin, an aminoglycoside that relaxes decoding specificity. Paromomycin has no effect if native tRNA Arg(ICG) is highly expressed, consistent with the idea that failure to efficiently decode CGA codons might occur in part due to rejection of the cognate tRNA Arg(ICG) . Furthermore, expression downstream from CGA repeats is improved by inactivation of RPL1B, one of two genes encoding the universally conserved ribosomal protein L1. The effects of rpl1b-Δ and of either paromomycin or tRNA Arg(ICG) on CGA decoding are additive, suggesting that the rpl1b-Δ mutant suppresses CGA inhibition by means other than increased acceptance of tRNA Arg(ICG) . Thus, inefficient decoding of CGA likely involves at least two independent defects in translation.

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Section: Discussionmentioning

confidence: 99%

Section: Protein Synthesis Is Discontinued At Cga Codon Repeatsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Translation of CGA codon repeats in yeast involves quality control components and ribosomal protein L1

Letzring

Wolf

Brule

et al. 2013

RNA

108

145

View full text Add to dashboard Cite

show abstract

“…Over the years, we have got to know that certain sequence features can trigger ribosome stalling. These are damaged bases (Cruz-Vera et al, 2004), stable stem-loop structures (Doma & Parker, 2006), rare codons (Letzring, Dean & Grayhack, 2010), mRNAs lacking stop codons (so called non-stop mRNAs) (Dimitrova et al, 2009), runs of codons that encode consecutive basic aminoacids (Kuroha et al, 2010;Brandman et al, 2012), or finally, runs of adenines encoding poly-lysine tracks Arthur et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

PATACSDB—the database of polyA translational attenuators in coding sequences

Habich

Djuranović

Szczęsny

2016

PeerJ Computer Science

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Recent additions to the repertoire of gene expression regulatory mechanisms are polyadenylate (polyA) tracks encoding for poly-lysine runs in protein sequences. Such tracks stall the translation apparatus and induce frameshifting independently of the effects of charged nascent poly-lysine sequence on the ribosome exit channel. As such, they substantially influence the stability of mRNA and the amount of protein produced from a given transcript. Single base changes in these regions are enough to exert a measurable response on both protein and mRNA abundance; this makes each of these sequences a potentially interesting case study for the effects of synonymous mutation, gene dosage balance and natural frameshifting. Here we present PATACSDB, a resource that contain a comprehensive list of polyA tracks from over 250 eukaryotic genomes. Our data is based on the Ensembl genomic database of coding sequences and filtered with algorithm of 12A-1 which selects sequences of polyA tracks with a minimal length of 12 A's allowing for one mismatched base. The PATACSDB database is accessible at: http://sysbio.ibb.waw.pl/patacsdb. The source code is available at http://github.com/habich/PATACSDB, and it includes the scripts with which the database can be recreated.

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Conserved functions of human Pelota in mRNA quality control of nonstop mRNA

et al. 2016

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Dom34-Hbs1 plays crucial roles in Nonstop Decay (NSD) and No-Go Decay (NGD). Here, we report a conserved function of human Pelota (hPelota) in mRNA quality control of nonstop mRNA. hPelota facilitated the expression of the nonstop products from GFP-Rz mRNA, which lacks a termination codon and a poly(A) tail, in exosome-defective mutant cells. hPelota promoted the dissociation of stalled ribosomes at the 3' end of GFP-Rz mRNA, and mutations in domain A diminished this activity. The hPelota-R45A mutant associated with ribosomes but was defective in peptide release. Finally, hPelota promoted the degradation of GFP-Rz mRNA and suppressed the sequential endonucleolytic cleavages caused by stalled ribosomes at the 3' end of mRNA in dom34∆ mutant cells.

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Receptor for activated C kinase 1 stimulates nascent polypeptide‐dependent translation arrest

Cited by 160 publications

References 25 publications

Translation of CGA codon repeats in yeast involves quality control components and ribosomal protein L1

Translation of CGA codon repeats in yeast involves quality control components and ribosomal protein L1

PATACSDB—the database of polyA translational attenuators in coding sequences

Conserved functions of human Pelota in mRNA quality control of nonstop mRNA

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