Lui, D. S. | Search bioRxiv

bioRxiv2021

Stimulation of immunity-linked genes by membrane disruption is linked to Golgi function and the ARF-1 GTPase

Immunity-linked genes (ILGs) are activated by pathogens but also may respond to imbalances in lipids. Why pathogen attack and metabolic changes both impact ILG activation is unclear. We find that ILGs are activated when membrane phosphatidylcholine ratios change in secretory organelles in C. elegans. RNAi targeting of the ADP-ribosylation factor ARF-1, which disrupts the Golgi, also activates ILG expression, suggesting that activation of this membrane stress response could occur outside the ER. Our data argue that ILG upregulation is a coordinated response to changes in trafficking resulting from intrinsic cues (changes in membrane lipids) or extrinsic stimulation (increased secretion during immune response). Indeed, a focused RNAi screen of ILGs uncovered defects in secretion of two GFP reporters as well as accumulation of a pathogen-responsive CUB-domain fusion protein. These results also suggests that genes shared between the classical pathogen responses and lipid stress may act to counteract stress on secretory function. TeaserPathogen response genes are also activated by lipid imbalances, which we suggest occurs because both processes put stress on the secretory pathway.

cell biology↗

bioRxiv2021

WormCat 2.0 defines characteristics and conservation of poorly annotated genes in Caenorhabditis elegans

Genome-wide measurement of mRNA or protein levels provides broad data sets for biological discovery. However, subsequent computational methods are essential for uncovering the functional implications of the data as well as intuitively visualizing the findings. Current computational tools are biased toward well-described pathways, limiting their utility for novel discovery. Recently, we developed an annotation and category enrichment tool for Caenorhabditis elegans genomic data, WormCat, that provides an intuitive visualization output. Unlike GO, which excludes genes with no annotation information, WormCat 2.0 retains these genes as a special UNASSIGNED category. Here, we show that the UNASSIGNED gene category enrichment exhibits tissue-specific expression patterns and include genes with biological functions. Poorly annotated genes have previously been considered to lack homologs in closely related species. Instead, we find that around 3% of the UNASSIGNED genes have poorly characterized human orthologs. These human orthologs are themselves have little annotation information. A recently developed method that incorporates lineage relationships (abSENSE) indicates that failure of BLAST to detect homology explains the apparent lineage specificity for many UNASSIGNED genes, suggesting that a larger subset could be related to human genes. WormCat provides an annotation strategy that allows association of UNASSIGNED genes with specific phenotypes and known pathways. Our analysis indicates that the UNASSIGNED gene category contains candidates that merit further functional study which could yield insight into understudied areas of biology.

genomics↗