PXD039739

PXD039739 is an original dataset announced via ProteomeXchange.

Title	Functional characterization of the RNA interference pathway in A. fumigatus reveals its potential for antifungal therapy
Description	The RNA interference (RNAi) pathway has evolved numerous functionalities in eukaryotes, with many on display in Kingdom Fungi. RNAi can regulate gene expression, facilitate drug resistance, or even be altogether lost to improve growth potential in some fungal pathogens. In the WHO fungal priority pathogen, Aspergillus fumigatus, the RNAi system is known to be intact and functional. To extend our limited understanding of A. fumigatus RNAi, we first investigated the genetic variation in RNAi-associated genes in a large collection of environmental and clinical genomes, where we found that RNAi is evolutionarily conserved even in clinical strains. Using endogenously expressed inverted-repeat transgenes complementary to both a conditionally essential gene and a nonessential gene, we determined that a subset of the RNAi componentry is active in inverted-repeat transgene silencing in conidia and mycelium. A multi-condition mRNA-seq analysis linked the A. fumigatus dicer-like enzymes and RNA-dependent RNA polymerases to regulation of conidial ribosome biogenesis genes; however, surprisingly few endogenous small RNAs were identified in conidia that could explain this broad change. Although RNAi was not clearly linked to growth or stress response defects in the RNAi knockouts, serial passaging of RNAi knockout strains for six generations resulted in lineages with diminished spore production over time, indicating that loss of RNAi can exert a fitness cost on the fungus. Cumulatively, A. fumigatus RNAi appears to play an active role in defense against double-stranded RNA species alongside a previously unappreciated housekeeping function in regulation of conidial ribosomal biogenesis genes.
HostingRepository	PRIDE
AnnounceDate	2023-02-18
AnnouncementXML	Submission_2023-02-18_08:30:37.967.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ThomasKrüger
SpeciesList	scientific name: Neosartorya fumigata (Aspergillus fumigatus); NCBI TaxID: 746128;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-30 03:39:15	ID requested
⏵ 1	2023-02-18 08:30:38	announced

Dataset with its publication pending

submitter keyword: RNA interference, Aspergillus fumigatus, RNA-based therapeutics, filamentous fungi, LC-MS/MS

Axel A.Brakhage
contact affiliation	Department of Molecular and Applied Microbiology Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute Jena Leibniz-HKI Adolf-Reichwein-Str. 23 Jena, Germany
contact email	axel.brakhage@leibniz-hki.de
lab head
ThomasKrüger
contact affiliation	Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute
contact email	thomas.krueger@leibniz-hki.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039739
     1. Label: PRIDE project
     2. Name: Functional characterization of the RNA interference pathway in A. fumigatus reveals its potential for antifungal therapy