Martineau, Celine N et al. MicroPubl Biol

Maynard, Claire A, Martineau, Celine N, Pujol, Nathalie

[MicroPubl Biol, 2022]

Fungal infection triggers the induction of antimicrobial peptide (AMP) genes in the epidermis (Pujol et al, 2008). We previously showed that this effect is suppressed by the mitochondrial unfolded protein response (UPRmt), which can beactivated by knockdown of select genes including the mitochondrial metalloprotease spg-7 (Zugasti et al, 2016). Here, we confirm that RNAi against spg-7 triggers the UPRmt and blocks AMP induction during infection, whereas infection itself doesnot trigger the UPRmt. ATFS-1 is a key factor in the UPRmt, mediating much of the associated transcriptional response. We find that, surprisingly, ATFS-1 is not required for the suppression of AMP induction provoked by spg-7(RNAi). These data show that the mitochondrial dysfunction that blocks the immune response upon infection or wounding is independent of ATFS-1.

Sin, Olga et al. (2015) International Worm Meeting "Identification of MOAG-2/LIR-3 as a regulator of protein aggregation."

Guryev, Victor, Reinke, Valerie, Sin, Olga, Willinge Prins, Romeo, Wang, Hai Hui, Martineau, Celine, Mata Cabana, Alejandro, Seinstra, Renee, Nollen, Ellen, Kudron, Michelle, de Jong, Tristan

[International Worm Meeting, 2015]

Aging-related protein aggregation is one of the hallmarks of neurodegenerative disorders such as Alzheimer, Parkinson and polyglutamine diseases. The cellular processes that drive protein aggregation in these diseases have remained largely unknown. Using a genetic screen in a C. elegans model for polyglutamine aggregation, we here identified modifier of aggregation 2 (moag-2). Mutation or partial deletion in this gene decreased the number of aggregates in our model. Additionally, moag-2/lir-3 mutants reduce the amount of SDS-resistant aggregates without changing total polyglutamine expression levels. We discovered that the causative gene of moag-2 is lir-3. moag-2/lir-3 encodes a protein with a predicted nuclear localization signal and two non-canonical C2H2 domains, which are homologous to the transcription factor for RNA polymerase III. The molecular function of MOAG-2/LIR-3 is unknown. Chromatin immunoprecipitation followed by sequencing data revealed that MOAG-2/LIR-3 is preferentially bound to promoter regions of non-coding RNA, namely tRNAs and snoRNAs. The consensus DNA sequence to which MOAG-2/LIR-3 is bound to corresponds to Box A and Box B motifs, which are recognized by the RNA Polymerase III machinery to initiate tRNA and snoRNA transcription. In fact, MOAG-2/LIR-3 is positioned in the same binding positions as the RNA Pol III complex, further suggesting a role for LIR-3 in non-coding RNA transcription. We are currently performing total RNA sequencing to reveal whether the aggregation phenotype displayed by the MOAG-2/LIR-3 mutants can be due to imbalanced RNA metabolism. By unraveling the role of moag-2/lir-3 we hope to get insight into how cells cope with aggregation-prone proteins.

Omi, Shizue et al. (2021) MicroPubl Biol

Thakur, Nishant, Omi, Shizue, Pujol, Nathalie, Zhang, Xing

[MicroPubl Biol, 2021]

The natural fungal pathogen Drechmeria coniospora pierces the worm's cuticle and its hyphae grow throughout the organism. In the epidermis, this triggers a rapid increase in the expression of genes from the nlp (for neuro-peptide-like protein) and cnc (caenacin) families. These genes encode structurally-related antimicrobial peptides (AMPs). We have defined major signalling pathways required for the regulation of nlp-29 gene expression. Two of them, one specific for infection and the second also activated by wounding, act upstream of a highly conserved p38 MAPK signalling cascade. The induction of cnc-2 upon infection, on the other hand, is independent of PMK-1/p38 MAPK, but requires DBL-1/TGF produced by certain neuronal cells, acting via a non-canonical TGF pathway in epidermal cells. The STAT transcription factor-like protein, STA-2, is essential for both the PMK-1/p38 MAPK, and DBL-1/TGF immune signalling pathways, to govern the transcriptional response to fungal infection in the epidermis (reviewed in Kim and Ewbank, 2018; Martineau et al., 2021).