A small RNA system ensures accurate homologous pairing and unpaired silencing of meiotic chromosomes

During meiosis, chromosomes with homologous partners undergo synaptonemal complex (SC)‐mediated pairing, while the remaining unpaired chromosomes are heterochromatinized through unpaired silencing. Mechanisms underlying homolog recognition during SC formation are still unclear. Here, we show that the Caenorhabditis elegans Argonaute proteins, CSR‐1 and its paralog CSR‐2, interacting with 22G‐RNAs, are required for synaptonemal complex formation with accurate homology. CSR‐1 in nuclei and meiotic cohesin, constituting the SC lateral elements, were associated with nonsimple DNA repeats, including minisatellites and transposons, and weakly associated with coding genes. CSR‐1‐associated CeRep55 minisatellites were expressing 22G‐RNAs and long noncoding (lnc) RNAs that colocalized with synaptonemal complexes on paired chromosomes and with cohesin regions of unpaired chromosomes. CeRep55 multilocus deletions reduced the efficiencies of homologous pairing and unpaired silencing, which were supported by the csr‐1 activity. Moreover, CSR‐1 and CSR‐2 were required for proper heterochromatinization of unpaired chromosomes. These findings suggest that CSR‐1 and CSR‐2 play crucial roles in homology recognition, achieving accurate SC formation between chromosome pairs and condensing unpaired chromosomes by targeting repeat‐derived lncRNAs. Synopsis It remains unclear how the homologous sequences of meiotic chromosomes, excluding the pairing center regions, are recognized during synaptonemal complex (SC) formation. This study describes a new model where an Argonaute‐dependent small RNA system is involved in homolog recognition during SC formation in C. elegans . Argonaute protein CSR‐1 and its paralog CSR‐2 interacting with 22G‐RNAs are required for SC formation between chromosome pairs with accurate homology. CSR‐1 and CSR‐2 are also involved in the condensation of unpaired chromosomes. CSR‐1 in nuclei and meiotic cohesin containing COH‐3/4 are associated with non‐simple DNA repeats and weakly with coding genes. CSR‐1 plays pleiotropic roles in the endogenous and exogenous RNAi pathways. Graphical Abstract Caenorhabditis elegans Argonaute proteins CSR‐1 and CSR‐2 mediate both synaptonemal complex formation and condensation of unpaired chromosomes by targeting repeat‐derived lncRNAs.