A CDK-11/SAP30BP/CYL-1 Complex Links Pre-mRNA Splicing to Developmental Cell Fate Decisions

Abstract Background Cyclin-dependent kinases (CDKs) and cyclins are integral to regulating cell cycle progression; however, many have additional roles in metazoans beyond controlling the cell cycle. One such cyclin, Cyclin L (CYL-1), has been shown to participate in pre-mRNA splicing through its interaction with CDK-11 in various cell lines. However, the in vivo functions of CYL-1 and its interacting partners during animal development remain poorly understood. Results In this study, we investigated the developmental roles of CYL-1 in Caenorhabditis elegans. Our findings revealed that CYL-1 is ubiquitously expressed in cell nuclei throughout development. By performing coimmunoprecipitation followed by mass spectrometry, we identified its interacting partners, confirming that CYL-1 forms complexes with both CDK-11.1 and CDK-11.2, as well as the highly conserved protein EEOL-1. Genetic analyses indicate that these four proteins are essential for mRNA biogenesis, with CDK-11.1 and CDK-11.2 functioning redundantly to regulate embryonic viability. Immunostaining assays demonstrated that CYL-1 plays a crucial role in both transcriptional initiation and elongation. Furthermore, using a cell fate marker, we demonstrated that CDK-11.1, CDK-11.2, and EEOL-1 are also involved in regulating cell fate specification. Conclusions Collectively, our findings establish that CYL-1 forms a complex with CDK-11.1, CDK-11.2, and EEOL-1, orchestrating mRNA biogenesis and cell fate determination during development. This research not only enhances our understanding of the multifaceted roles of CYL-1 but also sheds light on the intricate regulatory networks governing developmental processes.