Pre‐<scp>mRNA</scp> splicing is modulated by antifungal drugs in the filamentous fungus <i>Neurospora crassa</i>

Mendes, Niege Silva; Silva, Patrícia M.; Silva‐Rocha, Rafael; Martinez-Rossi, Nilce Maria; Rossi, Antônio

doi:10.1002/2211-5463.12047

Cited by 14 publications

(8 citation statements)

References 54 publications

(63 reference statements)

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“…The AS is a regulated molecular mechanism that increases protein diversity and therefore plays an important role in post-transcriptional events. Fungi responds to nutrient signalling, drug exposure, and environmental pH changes with AS 18 , 19 .…”

Section: Introductionmentioning

confidence: 99%

Transcriptome-wide survey of gene expression changes and alternative splicing in Trichophyton rubrum in response to undecanoic acid

Mendes

Bitencourt

Sanches

et al. 2018

Sci Rep

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While fatty acids are known to be toxic to dermatophytes, key physiological aspects of the Trichophyton rubrum response to undecanoic acid (UDA), a medium chain saturated fatty acid (C11:0), are not well understood. Thus, we analysed RNA-seq data from T. rubrum exposed to sub-lethal doses of UDA for 3 and 12 h. Three putative pathways were primarily involved in UDA detoxification: lipid metabolism and cellular membrane composition, oxidative stress, and pathogenesis. Biochemical assays showed cell membrane impairment, reductions in ergosterol content, and an increase in keratinolytic activity following UDA exposure. Moreover, we assessed differential exon usage and intron retention following UDA exposure. A key enzyme supplying guanine nucleotides to cells, inosine monophosphate dehydrogenase (IMPDH), showed high levels of intron 2 retention. Additionally, phosphoglucomutase (PGM), which is involved in the glycogen synthesis and degradation as well as cell wall biosynthesis, exhibited a significant difference in exon 4 usage following UDA exposure. Owing to the roles of these enzymes in fungal cells, both have emerged as promising antifungal targets. We showed that intron 2 retention in impdh and exon 4 skipping in pgm might be related to an adaptive strategy to combat fatty acid toxicity. Thus, the general effect of UDA fungal toxicity involves changes to fungal metabolism and mechanisms for regulating pre-mRNA processing events.

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Section: Introductionmentioning

confidence: 99%

Transcriptome-wide survey of gene expression changes and alternative splicing in Trichophyton rubrum in response to undecanoic acid

Mendes

Bitencourt

Sanches

et al. 2018

Sci Rep

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“…This gene codes for a C6 zinc finger transcription factor active in the regulation of two out of the five genes that act as specific regulators of conidiation in N. crassa ( Mendes et al , 2016 ) . Fluffy is expressed at a basal level in vegetative hyphae, and is transcriptionally activated in the aerial hyphae formation ( Bailey and Ebbole, 1998 ; Rerngsamran et al , 2005 ; Mendes et al , 2016 ). The expression pattern of PhiA and Fluffy genes in high Pi suggests that Δ pac-3 strain shows an attempt to restore conidiation by activating genes other than PhiA in the herein evaluated conditions.…”

Section: Discussionmentioning

confidence: 99%

“…The Fluffy gene is induced in response to sufficient Pi. This gene codes for a C6 zinc finger transcription factor active in the regulation of two out of the five genes that act as specific regulators of conidiation in N. crassa (Mendes et al, 2016). Fluffy is expressed at a basal level in vegetative hyphae, and is transcriptionally activated in the aerial hyphae formation (Bailey and Ebbole, 1998;Rerngsamran et al, 2005;Mendes et al, 2016).…”

Section: Dpac-3-mutation Is Responsive To Pi Variationmentioning

confidence: 99%

The PAC-3 transcription factor critically regulates phenotype-associated genes in Neurospora crassa

et al. 2020

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Transcription factors play an important role in fungal environmental adaptive process by promoting adjustment to challenging stimuli via gene modulation and activation of signaling networks. The transcription factor encoded by the pac-3/rim101/pacC gene is involved in pH regulation and is associated with a wide variety of cellular functions. The deletion of pac-3 affects fungal development. In Neurospora crassa, the Dpac-3 strain presents diminished aerial growth and reduced conidiation. However, the PAC-3-regulated genes associated with this altered phenotype have not been elucidated. In this study, we used RNA-seq to analyze the phenotypic plasticity induced after pac-3 deletion in the filamentous fungus N. crassa cultivated in media supplemented with sufficient or limited inorganic phosphate. Genes related to morphology, hyphal development, and conidiation were of particular interest in this study. Our results suggest a pac-3 dependency in gene regulation in a Pi-dependent manner. Furthermore, our analysis suggested that the fungus attempts to overcome the deletion effects in a Dpac-3 mutant through a complex combined regulatory mechanism. Finally, the modulatory responses observed in the Dpac-3 strain, a double mutant generated based on the Dmus-52 mutant strain, is strain-specific, highlighting that the phenotypic impact may be attributed to pac-3 absence despite the combined mus-52 deletion.

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“…IR is the leading AS mechanism in fungi, with critical roles in different fungal aspects, such as development, reproduction, mitochondrial functions, and signal transduction. However, its contribution to fungal biology still requires further studies [ 37 , 38 , 39 , 40 ]. Recently, using the same RNA-Seq data of the present work, our group published AS events in a T. rubrum strain.…”

Section: Discussionmentioning

confidence: 99%

STE20/PAKA Protein Kinase Gene Releases an Autoinhibitory Domain through Pre-mRNA Alternative Splicing in the Dermatophyte Trichophyton rubrum

Gomes

Bortolossi

Sanches

et al. 2018

IJMS

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Signaling pathways are highly diverse in filamentous fungi, allowing the cells to receive and process ambient information. Interaction of components from different pathways results in signaling networks. The mitogen-activated protein kinase (MAPK) pathway is dependent on phosphorylation that is accomplished by kinase proteins. Thus, the STE/PAK protein kinase family plays essential roles in MAPK signal transduction, regulating several cellular functions. The STE/PAK protein displays an autoinhibitory (Cdc42/Rac interactive binding—CRIB) domain on its N-terminal portion, which interacts with the C-terminal catalytic kinase domain. Based on current knowledge, for the STE/PAK kinase to be activated, molecular signals (e.g., interaction with the activated form of Rac1 and Cdc42 proteins) or proteolytic cleavage by caspase 3 is necessary. Both mechanisms release the kinase domain from the CRIB interaction. Here, we hypothesize a novel molecular mechanism for the activation of STE20/PAKA kinase in Trichophyton rubrum based on an alternative pre-mRNA splicing process. Our data suggest that, because of the retention of intron 1 of this gene, it is theoretically possible that the translation of STE20/PAKA kinase will be free of its autoinhibitory CRIB domain. These findings indicate a rapid response system to environmental changes. Furthermore, STE20/PAKA may be a potential T. rubrum virulence factor and an interesting target for new drugs against dermatophytes.

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Pre‐mRNA splicing is modulated by antifungal drugs in the filamentous fungus Neurospora crassa

Cited by 14 publications

References 54 publications

Transcriptome-wide survey of gene expression changes and alternative splicing in Trichophyton rubrum in response to undecanoic acid

Transcriptome-wide survey of gene expression changes and alternative splicing in Trichophyton rubrum in response to undecanoic acid

The PAC-3 transcription factor critically regulates phenotype-associated genes in Neurospora crassa

STE20/PAKA Protein Kinase Gene Releases an Autoinhibitory Domain through Pre-mRNA Alternative Splicing in the Dermatophyte Trichophyton rubrum

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