Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Protein kinase A regulated genes of Aspergillus fumigatus -FEBIT transcriptome analysis

ABSTRACT: Aspergillus fumigatus is a ubiquitous mould but also an opportunistic human pathogen causing life-threatening infections in immunocompromised patients. Survival of the fungus in different habitats depends on effective mechanisms of signal perception and transduction such as the cAMP dependent protein kinase A (PKA) pathway, which is involved in virulence of A. fumigatus. Here, by transcriptome analysis putative targets of this important signaling cascade were identified, revealing 632 differently regulated genes including 23 putative transcriptional regulators. The highest up-regulated transcription factor gene was located in the until now unknown fmp secondary metabolite gene cluster encoding an incomplete non-ribosomal peptide synthetase as core enzyme. Overexpression of the fmp cluster resulted in formation of fumipyrrole, which was not described as natural product yet. Although genes of the fmp cluster are transcribed in infected mouse lungs, deletion of its regulatory gene fmpR resulted in wild-type virulence in a murine infection model.

ORGANISM(S): Aspergillus fumigatus

SUBMITTER: Wolfgang Schmidt-Heck

PROVIDER: E-MTAB-2783 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNAse III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight, yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed 96% of miRNA genes were down-regulated and 37% of protein-coding genes were differentially expressed in GCKO testes. Interestingly, we observed preferential overexpression of genes on the sex chromosomes in GCKO testes, with more than 80% of the genes overlapping those proposed to undergo meiotic sex chromosome inactivation (MSCI) in the germ cells. Compared to WT, GCKO mice showed higher percentages of cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I), providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Furthermore, we observed fewer elongating spermatids with proper translational activation of transition protein 2 (Tnp2), protamine 1 and 2 (Prm1 and Prm2) in GCKO testes after step 12-14. Therefore, deleting Dicer1 in early postnatal germ cells causes misregulation of transcripts encoded by genes on the sex chromosomes, impairs meiotic progression and post-meiotic translational control and results in spermatogenic failure and infertility. Total RNA, including miRNAs, were purified from a total of six individual mouse samples. The tissue collected was obtained from wild-type (control; n=3) and Dicer1 germ cell knockout (mutant; n=3) testes on P18. One miRNA GCKO sample, M36, was determined to be of poor quality and was excluded from the study; thus, a total of five miRNA samples were analyzed.

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Protein kinase A regulated genes of Aspergillus fumigatus -FEBIT transcriptome analysis

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