Nab3 nuclear granule accumulation is driven by respiratory capacity

Hutchinson, Katherine Marie; Hunn, Jeremy C.; Reines, Daniel

doi:10.1007/s00294-022-01248-w

Cited by 3 publications

(3 citation statements)

References 47 publications

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“…mitochondrial defects (Hutchinson et al, 2022). In this light the significant upregulation of mitochondrial respiratory associated genes observed here indicates a similar mitochondrial involvement of Sky1 in C. albicans.…”

Section: Pathway Analyses Indicate Conserved Functions For Sky1 Where...supporting

confidence: 77%

“…These processes are consistent with reported functions of Sky1 in S. cerevisiae where this kinase has been described to regulate various steps in RNA maturation and transport ( Gilbert et al., 2001 ). In addition, a recent study has shown that the deletion of Sky1 in S. cerevisiae leads to mitochondrial defects ( Hutchinson et al., 2022 ). In this light the significant upregulation of mitochondrial respiratory associated genes observed here indicates a similar mitochondrial involvement of Sky1 in C. albicans .…”

Section: Resultsmentioning

confidence: 99%

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Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans

Luther

Brandt

Vylkova

et al. 2023

Front. Cell. Infect. Microbiol.

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Fungal infections are a major global health burden where Candida albicans is among the most common fungal pathogen in humans and is a common cause of invasive candidiasis. Fungal phenotypes, such as those related to morphology, proliferation and virulence are mainly driven by gene expression, which is primarily regulated by kinase signaling cascades. Serine-arginine (SR) protein kinases are highly conserved among eukaryotes and are involved in major transcriptional processes in human and S. cerevisiae. Candida albicans harbors two SR protein kinases, while Sky2 is important for metabolic adaptation, Sky1 has similar functions as in S. cerevisiae. To investigate the role of these SR kinases for the regulation of transcriptional responses in C. albicans, we performed RNA sequencing of sky1Δ and sky2Δ and integrated a comprehensive phosphoproteome dataset of these mutants. Using a Systems Biology approach, we study transcriptional regulation in the context of kinase signaling networks. Transcriptomic enrichment analysis indicates that pathways involved in the regulation of gene expression are downregulated and mitochondrial processes are upregulated in sky1Δ. In sky2Δ, primarily metabolic processes are affected, especially for arginine, and we observed that arginine-induced hyphae formation is impaired in sky2Δ. In addition, our analysis identifies several transcription factors as potential drivers of the transcriptional response. Among these, a core set is shared between both kinase knockouts, but it appears to regulate different subsets of target genes. To elucidate these diverse regulatory patterns, we created network modules by integrating the data of site-specific protein phosphorylation and gene expression with kinase-substrate predictions and protein-protein interactions. These integrated signaling modules reveal shared parts but also highlight specific patterns characteristic for each kinase. Interestingly, the modules contain many proteins involved in fungal morphogenesis and stress response. Accordingly, experimental phenotyping shows a higher resistance to Hygromycin B for sky1Δ. Thus, our study demonstrates that a combination of computational approaches with integration of experimental data can offer a new systems biological perspective on the complex network of signaling and transcription. With that, the investigation of the interface between signaling and transcriptional regulation in C. albicans provides a deeper insight into how cellular mechanisms can shape the phenotype.

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Section: Pathway Analyses Indicate Conserved Functions For Sky1 Where...supporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans

Luther

Brandt

Vylkova

et al. 2023

Front. Cell. Infect. Microbiol.

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“…Finally, the importance of Nab3 nuclear granules [ 95 ] deserves further investigations (also for Nrd1 PrLD) and anticipates new roles of NNS in the regulation of the stress response.…”

Section: Discussionmentioning

confidence: 99%

The Nrd1–Nab3–Sen1 transcription termination complex from a structural perspective

Chaves‐Arquero

Pérez‐Cañadillas

2023

Biochemical Society Transactions

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A substantial part of living cells activity involves transcription regulation. The RNA polymerases responsible for this job need to know ‘where/when' to start and stop in the genome, answers that may change throughout life and upon external stimuli. In Saccharomyces cerevisiae, RNA Pol II transcription termination can follow two different routes: the poly(A)-dependent one used for most of the mRNAs and the Nrd1/Nab3/Sen1 (NNS) pathway for non-coding RNAs (ncRNA). The NNS targets include snoRNAs and cryptic unstable transcripts (CUTs) generated by pervasive transcription. This review recapitulates the state of the art in structural biology and biophysics of the Nrd1, Nab3 and Sen1 components of the NNS complex, with special attention to their domain structures and interactions with peptide and RNA motifs, and their heterodimerization. This structural information is put into the context of the NNS termination mechanism together with possible prospects for evolution in the field.

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Post-transcriptional regulation shapes the transcriptome of quiescent budding yeast

Greenlaw,

Alavattam,

Tsukiyama

2023

Nucleic Acids Research

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To facilitate long-term survival, cells must exit the cell cycle and enter quiescence, a reversible non-replicative state. Budding yeast cells reprogram their gene expression during quiescence entry to silence transcription, but how the nascent transcriptome changes in quiescence is unknown. By investigating the nascent transcriptome, we identified over a thousand noncoding RNAs in quiescent and G1 yeast cells, and found noncoding transcription represented a larger portion of the quiescent transcriptome than in G1. Additionally, both mRNA and ncRNA are subject to increased post-transcriptional regulation in quiescence compared to G1. We found that, in quiescence, the nuclear exosome-NNS pathway suppresses over one thousand mRNAs, in addition to canonical noncoding RNAs. RNA sequencing through quiescent entry revealed two distinct time points at which the nuclear exosome controls the abundance of mRNAs involved in protein production, cellular organization, and metabolism, thereby facilitating efficient quiescence entry. Our work identified a previously unknown key biological role for the nuclear exosome-NNS pathway in mRNA regulation and uncovered a novel layer of gene-expression control in quiescence.

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Nab3 nuclear granule accumulation is driven by respiratory capacity

Cited by 3 publications

References 47 publications

Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans

Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans

The Nrd1–Nab3–Sen1 transcription termination complex from a structural perspective

Post-transcriptional regulation shapes the transcriptome of quiescent budding yeast

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