2018
DOI: 10.1083/jcb.201804163
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Ribosome biogenesis factor Ltv1 chaperones the assembly of the small subunit head

Abstract: The correct assembly of ribosomes from ribosomal RNAs (rRNAs) and ribosomal proteins (RPs) is critical, as indicated by the diseases caused by RP haploinsufficiency and loss of RP stoichiometry in cancer cells. Nevertheless, how assembly of each RP is ensured remains poorly understood. We use yeast genetics, biochemistry, and structure probing to show that the assembly factor Ltv1 facilitates the incorporation of Rps3, Rps10, and Asc1/RACK1 into the small ribosomal subunit head. Ribosomes from Ltv1-deficient y… Show more

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Cited by 49 publications
(108 citation statements)
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“…Although Nob1 depletion does not affect frameshifting, decoding, or stop codon recognition, start codon recognition is affected, leading to increased mistranslation at UUG codons relative to AUG codons ( Fig 1B). To test whether the remodeled proteome arising from these mistranslation events also affects stress resistance as previously observed from defects in translation arising from changes in ribosome composition or translation factors [7,42,43], we measured the effects from Nob1 depletion on growth in high-salt or caffeine-containing media. These data show that Nob1 depletion provides resistance to caffeine and high salt ( Fig 1C), consistent with a perturbation in protein synthesis.…”
Section: Nob1 Inhibits Mrna Recruitmentmentioning
confidence: 99%
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“…Although Nob1 depletion does not affect frameshifting, decoding, or stop codon recognition, start codon recognition is affected, leading to increased mistranslation at UUG codons relative to AUG codons ( Fig 1B). To test whether the remodeled proteome arising from these mistranslation events also affects stress resistance as previously observed from defects in translation arising from changes in ribosome composition or translation factors [7,42,43], we measured the effects from Nob1 depletion on growth in high-salt or caffeine-containing media. These data show that Nob1 depletion provides resistance to caffeine and high salt ( Fig 1C), consistent with a perturbation in protein synthesis.…”
Section: Nob1 Inhibits Mrna Recruitmentmentioning
confidence: 99%
“…To prevent misassembled ribosomes from reaching the translating pool, the precursor small (pre-40S) ribosomal subunit undergoes a series of quality-control checkpoints during late cytoplasmic maturation that verify proper ribosomal structure and function [5][6][7]. The importance of these checkpoints for cellular function is illustrated by the numerous diseases caused by haploinsufficiency or mutations in ribosomal proteins and assembly factors.…”
Section: Introductionmentioning
confidence: 99%
“…Together, these data argue for a role for Rps26-deficient cells in cancer progression. Furthermore, these data also demonstrate that cancer cells have found diverse means to effect loss of ribosomal protein stoichiometry, including changes in RP gene expression (Ajore et al, 2017;Guimaraes and Zavolan, 2016;Kulkarni et al, 2017;Vlachos, 2017), downregulation of the assembly factor Ltv1 leading to substoichiometric, Rps3, Rps10 and Asc1/RACK1 (Collins et al, 2018), and bypass of Rio1, leading to Rps26-deficient ribosomes.…”
Section: Bypassing the Rio1 Checkpoint Disturbs Protein Homeostasis Amentioning
confidence: 64%
“…Nob1 blocks mRNA recruitment to 20S pre-rRNA-containing ribosomes Nascent 40S subunits arrive in the cytoplasm bound to seven assembly factors, which block premature translation initiation on immature assembly intermediates by preventing the association of translation initiation factors (Strunk et al, 2012). These assembly factors are then released in a series of regulated steps that form part of a translation-like cycle, which couples the release of these factors to quality control steps (Collins et al, 2018;Ghalei et al, 2017;Strunk et al, 2012). Furthermore, when pre-mature ribosomes do escape into the translating pool, they are unable to support cell viability (Soudet et al, 2010;Strunk et al, 2012).…”
Section: Discussionmentioning
confidence: 99%
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