Roles of Dhh1 RNA helicase in yeast filamentous growth: Analysis of N-terminal phosphorylation residues and ATPase domains

Lee, Eunji; Jung, Daehee; Kim, Jinmi

doi:10.1007/s12275-020-0431-7

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Loss of DHH1 in S. cerevisiae downregulates STE12 translation leading to defects in pseudohyphal growth and mating [34,49,50]. Kinase signaling via Dhh1 phosphorylation sites are critical to pseudohyphal development in S. cerevisiae [34,51]. Our other PB factor of interest, Edc3 acts as a non-essential enhancer of mRNA decapping and PB scaffolding factor [42,43,52].…”

Section: Stochastic Transcriptional Noise Generates Different Phenoty...mentioning

confidence: 99%

Roles of P-body factors inCandida albicansfilamentation and stress response

Tosiano,

Lanni,

Mitchell

et al. 2024

Preprint

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Hyphal growth is strongly associated with virulence in the human fungal pathogenCandida albicans. While hyphal transcriptional networks have been the subject of intense study, relatively little is known about post-transcriptional regulation. Previous work reported that P Body (PB) factors Dhh1 and Edc3 were required for virulence and filamentation, suggesting an essential role for post-transcriptional regulation of these processes. However, the molecular roles of these factors have not been determined. To further study the function of PB factors in filamentation, we generated homozygous deletions ofDHH1andEDC3in the prototrophic strain SC5314 using CRISPR-Cas9. Homozygousdhh1deletion strongly impaired growth and altered filamentation, in addition to exhibiting unusual colony morphology in response to heat stress.Using RNA-seq, we foundDHH1deletion disrupts the regulation of thousands of genes under both yeast and hyphal growth conditions. This included upregulation of many stress response genes in the absence of stress, similar to deletion of theS. cerevisiae DHH1homolog. In contrast, we foundEDC3was not required for heat tolerance or filamentation. These results support a model in whichDHH1, but notEDC3, represses hyphal stress response transcripts in yeast and remodels the transcriptome during filamentation. Our paper supports distinct requirements for specific mRNA decay factors, bolstering evidence for post-transcriptional regulation of filamentation inC. albicans.Author summaryIn the dimorphic fungal pathogenC. albicans, the hyphal phenotype corresponds with pathogenicity. While transcriptional control of hyphal growth has been extensively studied, comparatively little is known about post-transcriptional regulation of this significant morphological shift. PB factors are associated with mRNA decay and translational repression. Here we investigate the roles of two PB factors in growth, filamentation, and gene expression. Although deletion of PB factor EDC3 did not impact growth or filamentation,dhh1Δ/Δhad greatly impaired growth and heat tolerance as well as unusual hyphal phenotypes. Additionally, we found that the transcriptomes ofdhh1Δ/Δyeast and hyphae were highly dysregulated. The extensive transcriptomic impacts of the absence of Dhh1 correlated with our phenotypic findings. Stress-associated genes were induced under non-stress conditions and the filamentation response was blunted under physiologically relevantin vitroconditions. We demonstrate that mRNA decay factors play distinct roles in regulatingC. albicansmorphology and that Dhh1 contributes to environmentally appropriate expression of the stress response and hyphal growth.

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Section: Stochastic Transcriptional Noise Generates Different Phenoty...mentioning

confidence: 99%

Roles of P-body factors inCandida albicansfilamentation and stress response

Tosiano,

Lanni,

Mitchell

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Likewise, lack of nutrients induces the dephosphorylation of Pat1, which forms a complex with Lsm1‐7 proteins and the binding of this complex to a subset of ATG mRNAs protects them from exosome‐dependent 3’‐5’ degradation [120]. Interestingly, Dhh1 promotes the translation of several other nonautophagy‐related mRNAs upon nutrient deprivation, and impairment of its activity results in significant defects during pseudohyphal growth [121]. This dual role of decapping activators that promote translation of some transcripts in the absence of Dcp2, could be employed by cells in order to amplify the stimulatory effect of impaired decapping on distinct mRNA regulons, favoring their translation under specific conditions.…”

Section: Biological Implications Of Decapping In Yeastsmentioning

confidence: 99%

Biological implications of decapping: beyond bulk mRNA decay

Borbolis

Syntichaki

2021

The FEBS Journal

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It is well established that mRNA steady-state levels do not directly correlate with transcription rate. This is attributed to the multiple posttranscriptional mechanisms, which control both mRNA turnover and translation within eukaryotic cells. One such mechanism is the removal of the 5' end cap structure of RNAs (decapping). This 5' cap plays a fundamental role in cellular functions related to mRNA processing, transport, translation, quality control, and decay, while its chemical modifications influence the fate of cytoplasmic mRNAs. Decapping is a highly controlled process, performed by multiple decapping enzymes, and regulated by complex cellular networks. In this review, we provide an updated synopsis of 5' end modifications and functions, and give an overview of mRNA decapping enzymes, presenting their enzymatic properties. Focusing on DCP2 decapping enzyme, a major component on the 5'-3' mRNA decay pathway, we describe cis-elements and transacting factors that affect its activity, substrate specificity, and cellular localization. Finally, we discuss current knowledge on the biological functions of mRNA decapping and decay factors, highlighting the major questions that remain to be addressed.

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The Complex Genetic Basis and Multilayered Regulatory Control of Yeast Pseudohyphal Growth

Kumar

2021

Annu. Rev. Genet.

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Eukaryotic cells are exquisitely responsive to external and internal cues, achieving precise control of seemingly diverse growth processes through a complex interplay of regulatory mechanisms. The budding yeast Saccharomyces cerevisiae provides a fascinating model of cell growth in its stress-responsive transition from planktonic single cells to a filamentous pseudohyphal growth form. During pseudohyphal growth, yeast cells undergo changes in morphology, polarity, and adhesion to form extended and invasive multicellular filaments. This pseudohyphal transition has been studied extensively as a model of conserved signaling pathways regulating cell growth and for its relevance in understanding the pathogenicity of the related opportunistic fungus Candida albicans, wherein filamentous growth is required for virulence. This review highlights the broad gene set enabling yeast pseudohyphal growth, signaling pathways that regulate this process, the role and regulation of proteins conferring cell adhesion, and interesting regulatory mechanisms enabling the pseudohyphal transition. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Roles of Dhh1 RNA helicase in yeast filamentous growth: Analysis of N-terminal phosphorylation residues and ATPase domains

Cited by 3 publications

References 29 publications

Roles of P-body factors inCandida albicansfilamentation and stress response

Roles of P-body factors inCandida albicansfilamentation and stress response

Biological implications of decapping: beyond bulk mRNA decay

The Complex Genetic Basis and Multilayered Regulatory Control of Yeast Pseudohyphal Growth

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