AUTHOR=Ow Maria C. , Nishiguchi Mailyn A. , Dar Abdul Rouf , Butcher Rebecca A. , Hall Sarah E. 

TITLE=RNAi-dependent expression of sperm genes in ADL chemosensory neurons is required for olfactory responses in Caenorhabditis elegans

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1396587

DOI=10.3389/fmolb.2024.1396587

ISSN=2296-889X

ABSTRACT=<p>Environmental conditions experienced early in the life of an animal can result in gene expression changes later in its life history. We have previously shown that <italic>C. elegans</italic> animals that experienced the developmentally arrested and stress resistant dauer stage (postdauers) retain a cellular memory of early-life stress that manifests during adulthood as genome-wide changes in gene expression, chromatin states, and altered life history traits. One consequence of developmental reprogramming in <italic>C. elegans</italic> postdauer adults is the downregulation of <italic>osm-9</italic> TRPV channel gene expression in the ADL chemosensory neurons resulting in reduced avoidance to a pheromone component, ascr#3. This altered response to ascr#3 requires the principal effector of the somatic nuclear RNAi pathway, the Argonaute (AGO) NRDE-3. To investigate the role of the somatic nuclear RNAi pathway in regulating the developmental reprogramming of ADL due to early-life stress, we profiled the mRNA transcriptome of control and postdauer ADL in wild-type and <italic>nrde-3</italic> mutant adults. We found 711 differentially expressed (DE) genes between control and postdauer ADL neurons, 90% of which are dependent upon NRDE-3. Additionally, we identified a conserved sequence that is enriched in the upstream regulatory sequences of the NRDE-3-dependent differentially expressed genes. Surprisingly, 214 of the ADL DE genes are considered “germline-expressed”, including 21 genes encoding the Major Sperm Proteins and two genes encoding the sperm-specific PP1 phosphatases, GSP-3 and GSP-4. Loss of function mutations in <italic>gsp-3</italic> resulted in both aberrant avoidance and attraction behaviors. We also show that an AGO pseudogene, Y49F6A.1 (<italic>wago-11</italic>), is expressed in ADL and is required for ascr#3 avoidance. Overall, our results suggest that small RNAs and reproductive genes program the ADL mRNA transcriptome during their developmental history and highlight a nexus between neuronal and reproductive networks in calibrating animal neuroplasticity.</p>