TORC1, stress and the nucleolus

Matos-Perdomo, Emiliano; Machín, Félix

doi:10.18632/aging.101456

Cited by 5 publications

(2 citation statements)

References 7 publications

(8 reference statements)

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“…Former stressors, with the exception of UV, are well-known inhibitors of the TORC1 complex [91,137,138], with an outcome (for some of them) of cease in new ribosome production [139]. Nonetheless, depletion of 60S ribosomes subunits leads to yeast life span extension [140].…”

Section: Torc1 Stress and The Size Of The Nucleolusmentioning

confidence: 99%

Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer

Matos-Perdomo

Machín

2019

Cells

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Once thought a mere ribosome factory, the nucleolus has been viewed in recent years as an extremely sensitive gauge of diverse cellular stresses. Emerging concepts in nucleolar biology include the nucleolar stress response (NSR), whereby a series of cell insults have a special impact on the nucleolus. These insults include, among others, ultra-violet radiation (UV), nutrient deprivation, hypoxia and thermal stress. While these stresses might influence nucleolar biology directly or indirectly, other perturbances whose origin resides in the nucleolar biology also trigger nucleolar and systemic stress responses. Among the latter, we find mutations in nucleolar and ribosomal proteins, ribosomal RNA (rRNA) processing inhibitors and ribosomal DNA (rDNA) transcription inhibition. The p53 protein also mediates NSR, leading ultimately to cell cycle arrest, apoptosis, senescence or differentiation. Hence, NSR is gaining importance in cancer biology. The nucleolar size and ribosome biogenesis, and how they connect with the Target of Rapamycin (TOR) signalling pathway, are also becoming important in the biology of aging and cancer. Simple model organisms like the budding yeast Saccharomyces cerevisiae, easy to manipulate genetically, are useful in order to study nucleolar and rDNA structure and their relationship with stress. In this review, we summarize the most important findings related to this topic.

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Section: Torc1 Stress and The Size Of The Nucleolusmentioning

confidence: 99%

Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer

Matos-Perdomo

Machín

2019

Cells

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“…A fourth major finding of the current study is that the High Mobility Group protein Hmo1, that is involved in TOR signaling, negatively regulates mitotic rDNA condensation. Inhibition of TOR by rapamycin causes nucleolar contraction, condensin loading on to rDNA during interphase, and also promotes rDNA hypercondensation in both pre-anaphase and anaphase-arrested cells (Tsang et al, 2007; de los Santos-Vas et al, 2017; Matos-Perdomo and Machín, 2018a; Matos-Perdomo and Machín, 2018b). Thus, TOR inhibition might trigger increased condensation of rDNA through Hmo1.…”

Section: Discussionmentioning

confidence: 99%

Promotion of hyperthermic-induced rDNA hypercondensation inSaccharomyces cerevisiae

Shen

Skibbens

2019

Preprint

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Ribosome biogenesis is tightly regulated through stress-sensing pathways that impact genome stability, aging and senescence. In Saccharomyces cerevisiae, ribosomal RNAs are transcribed from rDNA located on the right arm of chromosome XII. Numerous studies reveal that rDNA decondenses into a puff-like structure during interphase and condenses into a tight loop-like structure during mitosis. Intriguingly, a novel and additional mechanism of increased mitotic rDNA compaction (termed hypercondensation) was recently discovered that occurs in response to temperature stress (hyperthermic-induced) and is rapidly reversible. Here, we report that neither changes in condensin nor cohesin binding dynamics appear to play a critical role in hyperthermic-induced rDNA hypercondensation – differentiating this architectural state from normal mitotic condensation (requiring cohesins and condensins) and the premature condensation (requiring condensins) that occurs during interphase in response to nutrient starvation. A candidate genetic approach revealed that deletion of either Hsp82 or Hsc82 (Hsp90 heat shock paralogs) result in significantly reduced hyperthermic-induced rDNA hypercondensation. Intriguingly, Hsp inhibitors do not impact rDNA hypercondensation. In combination, these findings suggest that Hsp90 either stabilizes client proteins, which are sensitive to very transient thermic challenges, or directly promotes rDNA hypercondensation during preanaphase. Our findings further reveal that the high mobility group protein Hmo1 is a negative regulator of mitotic rDNA condensation, distinct from its role in promoting premature-condensation of rDNA during interphase upon nutrient starvation.

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TORC1, stress and the nucleolus

Cited by 5 publications

References 7 publications

Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer

Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer

Promotion of hyperthermic-induced rDNA hypercondensation inSaccharomyces cerevisiae

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