Abstract

Accurate chromosome segregation during meiosis depends on precise homolog pairing. This process is driven by a series of specialized proteins that link chromosomes to cytoskeletal motors and coordinate chromosome movement for homolog recognition and alignment. Here, we identified RBPL-1, the Caenorhabditis elegans homolog of RBBP6, as a germline-expressed regulator essential for proper homolog pairing and associated nuclear reorganization. Depletion of RBPL-1 impaired the formation of clusters of the LINC complex and CHK-2 kinase within the nuclear periphery. Furthermore, we showed that RBPL-1 regulates the protein abundance of ZIM/HIM-8-family proteins and PLK-2 kinase, two critical mediators of homolog pairing. Notably, RBPL-1's role in homolog pairing is independent of the RING finger domain and Zn knuckle motif, which are proposed to mediate ubiquitination and alternative polyadenylation (APA)/mRNA processing respectively. Instead, we reveal that the evolutionarily conserved yet functionally enigmatic DWNN domain is essential for RBPL-1's function in homolog pairing. In summary, our findings demonstrate that RBPL-1 contributes to meiotic homolog pairing through its DWNN domain, by mediating nuclear reorganization and controlling the abundance of essential pairing factors. Graphical During meiotic prophase, the Caenorhabditis elegans RBBP6 homolog RBPL-1 and its conserved DWNN domain promote chromosome clustering and homolog pairing by maintaining the protein levels of ZIM/HIM-8 proteins and PLK-2 kinase; loss of RBPL-1 or the DWNN domain reduces these key factors and impairs chromosome pairing and synapsis.