Sub1 and RNAPII, until termination does them part

Calvo, Olga

doi:10.1080/21541264.2017.1333558

Cited by 7 publications

(10 citation statements)

References 55 publications

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“…The human positive cofactor 4 (PC4) or Sub1 in yeast has recently attracted great attention of researchers worldwide (F. Liao et al, 2020; Mondal et al, 2019; Sikder et al, 2019). PC4 has been considered as an evolutionarily conserved transcriptional co‐activator since the first identification (Ge & Roeder, 1994), which is involved in transcriptional activation (Calvo, 2018), oxidative stress (Yu et al, 2016) histone modification (Sikder et al, 2019), and maintaining genomic stability (Garavis & Calvo, 2017). In this study, for the first time, we find that PC4 is increased and becomes activated with age, and transgenic expression of PC4 disturbs mTOR‐regulated proteostasis and causes global accelerated ageing by promoting histone acetylation.…”

Section: Introductionmentioning

confidence: 99%

Acceleration of ageing via disturbing mTOR‐regulated proteostasis by a new ageing‐associated gene PC4

Chen

Liao

et al. 2021

Aging Cell

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Research on ageing‐associated genes is important for investigating ageing and anti‐ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3‐HDAC complex and inhibits its deacetylated activity, leads to hyper‐acetylation of the histones at the promoters of mTOR‐related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing‐associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing.

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Section: Introductionmentioning

confidence: 99%

Acceleration of ageing via disturbing mTOR‐regulated proteostasis by a new ageing‐associated gene PC4

Chen

Liao

et al. 2021

Aging Cell

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“…Sub1, a conserved factor (yeast homolog of mammalian PC4) was previously found to facilitate Pol II transcription in a variety of ways ( Garavís and Calvo, 2017 ; Calvo, 2018 ), to be recruited to the PIC ( Sikorski et al, 2011 ), and to alter accessibility of promoter single-stranded DNA, consistent with initiation functions ( Lada et al, 2015 ). sub1∆ has extensive genetic interactions with initiation factors and itself causes TSSs to shift downstream ( Wu et al, 1999 ; Knaus et al, 1996 ; Braberg et al, 2013 ; Koyama et al, 2008 ), though its actual role in initiation is unknown.…”

Section: Resultsmentioning

confidence: 99%

“…Consistently, double mutants shifted ADH1 TSS distributions to similar extent as the tfg2∆146-180 single mutant (Figure 7C, Figure 7 -Figure supplement 1) as predicted for an increase in initiation efficiency buffering against effects of increase in scanning processivity. Sub1, a conserved factor (yeast homolog of mammalian PC4) was previously found to facilitate Pol II transcription in a variety of ways 70,71 , to be recruited to the PIC 72 , and to alter accessibility of promoter single-stranded DNA, consistent with initiation functions 73 . sub1∆ has extensive genetic interactions with initiation factors and itself causes TSSs to shift downstream 29,38,50,74 , though its actual role in initiation is unknown.…”

Section: Genetic Interactions Between Initiation Factors and Ssl2 Alleles Suggest Distinct Roles For Ssl2 And Other Factors In Tss Scannimentioning

confidence: 99%

Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae

Zhao

Vvedenskaya

Lai

et al. 2021

eLife

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In Saccharomyces cerevisiae, RNA Polymerase II (Pol II) selects transcription start sites (TSS) by a unidirectional scanning process. During scanning, a preinitiation complex (PIC) assembled at an upstream core promoter initiates at select positions within a window ~40-120 basepairs downstream. Several lines of evidence indicate that Ssl2, the yeast homolog of XPB and an essential and conserved subunit of the general transcription factor (GTF) TFIIH, drives scanning through its DNA-dependent ATPase activity, therefore potentially controlling both scanning rate and scanning extent (processivity). To address questions of how Ssl2 functions in promoter scanning and interacts with other initiation activities, we leveraged distinct initiation-sensitive reporters to identify novel ssl2 alleles. These ssl2 alleles, many of which alter residues conserved from yeast to human, confer either upstream or downstream TSS shifts at the model promoter ADH1 and genome-wide. Specifically, tested ssl2 alleles alter TSS selection by increasing or narrowing the distribution of TSSs used at individual promoters. Genetic interactions of ssl2 alleles with other initiation factors are consistent with ssl2 allele classes functioning through increasing or decreasing scanning processivity but not necessarily scanning rate. These alleles underpin a residue interaction network that likely modulates Ssl2 activity and TFIIH function in promoter scanning. We propose that the outcome of promoter scanning is determined by two functional networks, the first being Pol II activity and factors that modulate it to determine initiation efficiency within a scanning window, and the second being Ssl2/TFIIH and factors that modulate scanning processivity to determine the width of the scanning widow.

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“…Sub1, a conserved factor (yeast homolog of mammalian PC4) was previously found to facilitate Pol II transcription in a variety of ways 70, 71 , to be recruited to the PIC 72 , and to alter accessibility of promoter single-stranded DNA, consistent with initiation functions 73 . sub1 Δ has extensive genetic interactions with initiation factors and itself causes TSSs to shift downstream 29, 38, 50, 74 , We found sub1 Δ to confer a His + phenotype for the imd2Δ::HIS3 initiation reporter 41 and furthermore found that Pol II GOF alleles appeared epistatic to sub1 Δ, leading to the proposal that sub1 Δ effects in initiation were distinct from TFIIB or TFIIF alleles 39 .…”

Section: Resultsmentioning

confidence: 99%

Ssl2/TFIIH function in Transcription Start Site Scanning by RNA Polymerase II in Saccharomyces cerevisiae

Zhao

Vvedenskaya

Lai

et al. 2021

Preprint

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Ssl2, as an essential subunit of the RNA Polymerase II (Pol II) general transcription factor TFIIH, promotes melting of promoter DNA through its ATPase-dependent DNA translocase activity within the Pol II pre-initiation complex. In Saccharomyces cerevisiae, after DNA melting, Ssl2 is proposed to drive Pol II scanning downstream for usable transcription start sites (TSSs) through this same ATP-dependent DNA translocase activity. However, how Pol II catalytic activity or activities of other general transcription factors integrate with Ssl2/TFIIH activity for promoter scanning and what ways Ssl2 modulates TSS selection by scanning have not been well studied. Here, we report the identification of ssl2 alleles conferring phenotypes in vivo consistent with altered Pol II initiation. We find that these ssl2 alleles alter TSS selection by scanning in ways that are distinct from how changes to Pol II or other GTF activities alter TSS selection by scanning. Specific predictions arise for interactions among initiation mutants depending on whether they function in promoter scanning through modulating initiation at an individual TSS or if they control the probability that a TSS is reached during the scanning process (scanning processivity). We test these predictions genetically and through analysis of transcription output at ADH1 and at promoters across the genome. Our data support a model whereby ssl2 alleles alter Ssl2 processivity and therefore the probability that TSSs are scanned. Examination of TSS usage genome-wide finds global effects of ssl2 alleles on TSS usage and the potential coupling of Pol II activity and Ssl2/TFIIH processivity during scanning. We propose that the initiation by promoter scanning is determined by the interaction of two functional networks, one controlling initiation efficiency and one controlling the processivity of scanning.

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Sub1 and RNAPII, until termination does them part

Cited by 7 publications

References 55 publications

Acceleration of ageing via disturbing mTOR‐regulated proteostasis by a new ageing‐associated gene PC4

Acceleration of ageing via disturbing mTOR‐regulated proteostasis by a new ageing‐associated gene PC4

Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae

Ssl2/TFIIH function in Transcription Start Site Scanning by RNA Polymerase II in Saccharomyces cerevisiae

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