The Spt7 subunit of the SAGA complex is required for the regulation of lifespan in both dividing and nondividing yeast cells

Lim, Suji; Ahn, Hyo‐Jeong; Duan, Ruxin; Liu, Yan; Ryu, Hong‐Yeoul; Ahn, Seong Hoon

doi:10.1016/j.mad.2021.111480

Cited by 9 publications

(19 citation statements)

References 65 publications

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“…SAGA plays multiple roles in transcription, including histone modification and RNA metabolism [14], and the individual loss of its components differently affects RLS in yeast [9, 11, 12], implying that the complex network of subunits needs to ensure a normal lifespan. Additionally, RLS is distinctly influenced by null mutants of nucleoporin proteins [32, 33].…”

Section: Discussionmentioning

confidence: 99%

“…The images were acquired using an AxioCam HRm mounted on an Axio Observer. Z1 microscope with a Plan-Apochromat 100×/1.40 Oil DIC M27 objective lens, as reported previously [12]. Zeiss Filter Sets 38 HE (489038-9901-000), 20 (488020-9901-000), and 49 (488049-9901-000) were used to observe the fluorescence of GFP (excitation, 488 nm; emission, 509 nm), Cy3 (excitation, 549 nm; emission, 562 nm), and 4′,6-diamidino-2-phenylindole (DAPI; excitation, 359 nm; emission, 463 nm), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…The rate of marker loss through the unequal recombination of an ADE2 marker inserted into the rDNA array was measured as reported previously [12, 65]. Cells grown to 1.0 OD 600 were plated at a density of ∼400 cells per SC plate containing a low adenine concentration (27 μM).…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the heterozygous mutant GCN5 or NGG1 , a linker protein between Gcn5 and SAGA [10], leads to an increase in RLS [9]. However, yeast cells entirely lacking each component in the SAGA HAT module either do not exhibit an extended lifespan or rather show a decreased lifespan [11, 12]. Loss of Ubp8, Sgf73, or Sgf11 in the SAGA DUB module exceptionally extends RLS in a Sir2-dependent manner by enhancing telomeric silencing and promoting rDNA stability [11], whereas lacking the components in the SAGA SPT module mostly leads to a decrease in both RLS and CLS [12].…”

Section: Introductionmentioning

confidence: 99%

“…However, yeast cells entirely lacking each component in the SAGA HAT module either do not exhibit an extended lifespan or rather show a decreased lifespan [11, 12]. Loss of Ubp8, Sgf73, or Sgf11 in the SAGA DUB module exceptionally extends RLS in a Sir2-dependent manner by enhancing telomeric silencing and promoting rDNA stability [11], whereas lacking the components in the SAGA SPT module mostly leads to a decrease in both RLS and CLS [12]. In particular, Spt7 in the SAGA SPT module is indispensable for a normal lifespan by maintaining genome stability and overall mRNA expression, and it is independent of Sir2 [12].…”

Section: Introductionmentioning

confidence: 99%

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Sus1 maintains a normal lifespan through regulation of TREX-2 complex-mediated mRNA export

Lim

Liu

Rhie

et al. 2022

Preprint

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Eukaryotic gene expression requires multiple cellular events, including transcription and RNA processing and transport. Sus1, a common subunit in both the Spt-Ada-Gcn5 acetyltransferase (SAGA) and transcription and export complex-2 (TREX-2) complexes, is a key factor in coupling transcription activation to mRNA nuclear export. Here we present that the SAGA DUB module and TREX-2 regulates distinctly yeast replicative lifespan in a Sir2-dependent and -independent manner, respectively. The growth and lifespan impaired by SUS1 loss depend on TREX-2 but not on the SAGA DUB module. Notably, an increased dosage of the mRNA export factors Mex67 and Dbp5 rescues the growth defect, shortened lifespan, and nuclear accumulation of poly(A)+ RNA in sus1Δ cells, suggesting that boosting the mRNA export process restores the mRNA transport defect and damage in the growth and lifespan of sus1Δ cells. Moreover, Sus1 is required for the proper association of Mex67 and Dbp5 with the nuclear rim. Together, these data suggest that Sus1 links transcription and mRNA nuclear export to the lifespan control pathway, indicating that prevention of an abnormal accumulation of nuclear RNA is necessary for maintaining a normal lifespan.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Sus1 maintains a normal lifespan through regulation of TREX-2 complex-mediated mRNA export

Lim

Liu

Rhie

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

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Senescence in yeast is associated with chromosome XII cleavage rather than ribosomal DNA circle accumulation

Zylstra

Horkai

Hadj‐Moussa

et al. 2022

Preprint

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The massive accumulation of extrachromosomal ribosomal DNA circles (ERCs) in yeast mother cells has been long cited as the primary driver of replicative ageing. ERCs arise through ribosomal DNA (rDNA) recombination and a wealth of genetic data connects rDNA instability to shortened lifespan and other ageing pathologies. However, we understand little about the molecular effects of ERC accumulation. Here we analysed the widespread disruption of gene expression that accompanies yeast ageing, and unexpectedly found this to be independent of ERCs. Furthermore, we found no evidence of gene expression differences in the presence of ERCs that might indicate stress responses or metabolic feedback. Accumulation of Tom70-GFP, a marker for the onset of cell division defects at the Senescence Entry Point (SEP), also correlated poorly to ERC abundance but displayed a transcriptomic signature separable from age. This signature is dominated by copy number amplification of a region of chromosome XII between the rDNA and the telomere (ChrXIIr) which arises in aged cells due to rDNA instability, but through a different mechanism to ERCs. Our findings implicate ChrXIIr, rather than ERCs, as the primary driver of senescence during budding yeast ageing.

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Tho2‐mediated escort of Nrd1 regulates the expression of aging‐related genes

Liu,

Park,

Lim

et al. 2024

Aging Cell

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The relationship between aging and RNA biogenesis and trafficking is attracting growing interest, yet the precise mechanisms are unknown. The THO complex is crucial for mRNA cotranscriptional maturation and export. Herein, we report that the THO complex is closely linked to the regulation of lifespan. Deficiencies in Hpr1 and Tho2, components of the THO complex, reduced replicative lifespan (RLS) and are linked to a novel Sir2‐independent RLS control pathway. Although transcript sequestration in hpr1Δ or tho2Δ mutants was countered by exosome component Rrp6, loss of this failed to mitigate RLS defects in hpr1Δ. However, RLS impairment in hpr1Δ or tho2Δ was counteracted by the additional expression of Nrd1‐specific mutants that interacted with Rrp6. This effect relied on the interaction of Nrd1, a transcriptional regulator of aging‐related genes, including ribosome biogenesis or RNA metabolism genes, with RNA polymerase II. Nrd1 overexpression reduced RLS in a Tho2‐dependent pathway. Intriguingly, Tho2 deletion mirrored Nrd1 overexpression effects by inducing arbitrary Nrd1 chromatin binding. Furthermore, our genome‐wide ChIP‐seq analysis revealed an increase in the recruitment of Nrd1 to translation‐associated genes, known to be related to aging, upon Tho2 loss. Taken together, these findings underscore the importance of Tho2‐mediated Nrd1 escorting in the regulation of lifespan pathway through transcriptional regulation of aging‐related genes.

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The Spt7 subunit of the SAGA complex is required for the regulation of lifespan in both dividing and nondividing yeast cells

Cited by 9 publications

References 65 publications

Sus1 maintains a normal lifespan through regulation of TREX-2 complex-mediated mRNA export

Sus1 maintains a normal lifespan through regulation of TREX-2 complex-mediated mRNA export

Senescence in yeast is associated with chromosome XII cleavage rather than ribosomal DNA circle accumulation

Tho2‐mediated escort of Nrd1 regulates the expression of aging‐related genes

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