The mechanism of homologous chromosome recognition and pairing facilitated by chromosome-tethered protein-RNA condensates

Pairing of homologous chromosomes during meiosis is crucial for successful sexual reproduction. Previous studies have shown that the fission yeast sme2 RNA, a meiosis-specific long noncoding RNA (lncRNA), accumulates at the sme2 locus and plays a key role in mediating robust pairing during meiosis. Several RNA-binding proteins accumulate at the sme2 and other lncRNA gene loci in conjunction with the lncRNAs transcribed from these loci. These lncRNA-protein complexes form condensates that exhibit phase separation properties on chromosomes and are necessary for robust pairing of homologous chromosomes. To further understand the mechanisms by which phase separation affects homologous chromosome pairing, we conducted an in vitro phase separation assay with the sme2 RNA-associated proteins (Smps) and RNAs. Our research has revealed that one of the Smps, Seb1, exhibits phase separation, which is enhanced by the addition of another Smp, Rhn1, and significantly increased by the addition of purified RNAs. Additionally, we have found that RNAs protect Smp condensates from treatment with 1,6-hexanediol. The Smp condensates containing different types of RNA display distinct FRAP profiles, and the Smp condensates containing the same type of RNA tend to fuse together more efficiently than those containing different types of RNA. Taken together, these results indicate that the RNA species in condensates determine their physical properties and suggest that regional RNA-Smp condensates with distinct properties ensure the pairing of homologous chromosomes.