title: A Small RNA-Catalytic Argonaute Pathway Tunes Germline Transcript Levels to Ensure Embryonic Divisions.
abstract: Multiple division cycles without growth are a characteristic feature of early embryogenesis. The female germline loads proteins and RNAs into oocytes to support these divisions, which lack many quality control mechanisms operating in somatic cells undergoing growth. Here, we describe a small RNA-Argonaute pathway that ensures early embryonic divisions in C. elegans by employing catalytic slicing activity to broadly tune, instead of silence, germline gene expression. Misregulation of one target, a kinesin-13 microtubule depolymerase, underlies a major phenotype associated with pathway loss. Tuning of target transcript levels is guided by the density of homologous small RNAs, whose generation must ultimately be related to target sequence. Thus, the tuning action of a small RNA-catalytic Argonaute pathway generates oocytes capable of supporting embryogenesis. We speculate that the specialized nature of germline chromatin led to the emergence of small RNA-catalytic Argonaute pathways in the female germline as a post-transcriptional control layer to optimize oocyte composition.
authors.affiliation: Ludwig Institute for Cancer Research, San Diego, CA 92093, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Adina
authors.initials: A
authors.lastname: Gerson-Gurwitz
authors.affiliation: Ludwig Institute for Cancer Research, San Diego, CA 92093, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Shaohe
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; UCSD Stem Cell Program & Sanford Consortium for Regenerative Medicine, Institute for Genomic Medicine, La Jolla, CA 92093, USA.
authors.forename: Shashank
authors.initials: S
authors.lastname: Sathe
authors.affiliation: Ludwig Institute for Cancer Research, San Diego, CA 92093, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Green
authors.affiliation: Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA; UCSD Stem Cell Program & Sanford Consortium for Regenerative Medicine, Institute for Genomic Medicine, La Jolla, CA 92093, USA.
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
authors.affiliation: Ludwig Institute for Cancer Research, San Diego, CA 92093, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
authors.affiliation: Ludwig Institute for Cancer Research, San Diego, CA 92093, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: abdesai@ucsd.edu.
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002455:Cell Division; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D047108:Embryonic Development; D005260:Female; D016547:Kinesins / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional
chemical_list: D060565:Argonaute Proteins; C544459:CSR-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C502821:klp-7 protein, C elegans; D016547:Kinesins
keywords: 22G RNA; Argonaute; C. elegans; CSR-1; centromere; chromosome; embryogenesis; fertility; germline; maternal load; oogenesis; small RNA