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Comments on Renaud, Mathias et al. (2021) International Worm Meeting "Father knows best: Small RNA-mediated regulation of male fertility and paternal epigenetic inheritance in Caenorhabditis elegans" (0)
Overview
Renaud, Mathias, Charlesworth, Amanda G., Seroussi, Uri, Woock, Jenna, & Claycomb, Julie M. (2021). Father knows best: Small RNA-mediated regulation of male fertility and paternal epigenetic inheritance in Caenorhabditis elegans presented in International Worm Meeting. Unpublished information; cite only with author permission.
With diverse roles in essential biological processes including development, genome stability, and fertility, small RNA (sRNA) pathways are key regulators of gene expression. sRNAs direct sequence-specific gene regulation by associating with effector Argonaute proteins (AGOs) to either degrade, inhibit translation, or promote expression of target transcripts. With a robust developmental program and an expanded group of 19 AGOs, Caenorhabditis elegans is a superb system to study these highly conserved regulatory mechanisms. Our lab has systematically characterized the expression and sRNA populations associated with all 19 AGOs in C. elegans. In doing so, we identified four AGOs expressed in the gonad only during spermatogenesis, and nine AGOs expressed constitutively in the germline. Although it is well established that sRNA pathways are essential for fertility in multiple organisms, the bulk of worm sRNA research has focused on roles in oogenesis. Therefore, we aim to understand how these 13 AGO/sRNA pathways contribute to proper sperm development and paternal epigenetic inheritance. By assessing trans-generational fertility in single and multiple spermatogenesis-specific ago mutants, we have observed stress-induced reductions in fertility that can be rescued by mating to wild-type males, pointing to defects in spermatogenesis. Our current efforts are focused on understanding the molecular mechanisms by which the spermatogenesis AGOs contribute to the development and differentiation of fertile sperm. Because mature spermatids can carry several potential epigenetic couriers to progeny, including chromatin modifications and sRNAs, we also aim to understand which AGOs and sRNAs are passed from father to progeny via sperm. Using our set of GFP-tagged AGOs, we determined that only two AGOs are packaged into mature sperm, one in the nucleus and one cytoplasmically. Collectively, our work will define new pathways and gene regulatory modes that contribute to male fertility and epigenetic inheritance.
Affiliation:
- Department of Molecular Genetics, University of Toronto, Toronto, Canada