title: Comparative functional characterization of the CSR-1 22G-RNA pathway in Caenorhabditis nematodes.
abstract: As a champion of small RNA research for two decades, Caenorhabditis elegans has revealed the essential Argonaute CSR-1 to play key nuclear roles in modulating chromatin, chromosome segregation and germline gene expression via 22G-small RNAs. Despite CSR-1 being preserved among diverse nematodes, the conservation and divergence in function of the targets of small RNA pathways remains poorly resolved. Here we apply comparative functional genomic analysis between C. elegans and Caenorhabditis briggsae to characterize the CSR-1 pathway, its targets and their evolution. C. briggsae CSR-1-associated small RNAs that we identified by immunoprecipitation-small RNA sequencing overlap with 22G-RNAs depleted in cbr-csr-1 RNAi-treated worms. By comparing 22G-RNAs and target genes between species, we defined a set of CSR-1 target genes with conserved germline expression, enrichment in operons and more slowly evolving coding sequences than other genes, along with a small group of evolutionarily labile targets. We demonstrate that the association of CSR-1 with chromatin is preserved, and show that depletion of cbr-csr-1 leads to chromosome segregation defects and embryonic lethality. This first comparative characterization of a small RNA pathway in Caenorhabditis establishes a conserved nuclear role for CSR-1 and highlights its key role in germline gene regulation across multiple animal species.
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, USA 01605.
authors.forename: Shikui
authors.initials: S
authors.lastname: Tu
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8.
authors.forename: Monica Z
authors.initials: MZ
authors.lastname: Wu
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, USA 01605.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Ecology & Evolutionary Biology, University of Toronto, Toronto, ON, Canada M5S 3B2.
authors.forename: Asher D
authors.initials: AD
authors.lastname: Cutter
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, USA 01605.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8 zhiping.weng@umassmed.edu.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Claycomb
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D002107:Caenorhabditis / Q000235:genetics* / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000145:classification; D002843:Chromatin / Q000378:metabolism; D020090:Chromosome Segregation; D005786:Gene Expression Regulation; D015801:Helminth Proteins / Q000378:metabolism*; D058727:RNA, Small Untranslated / Q000378:metabolism*
chemical_list: D060565:Argonaute Proteins; C544459:CSR-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D015801:Helminth Proteins; D058727:RNA, Small Untranslated