A CDK-11/SAP30BP/CYL-1 complex links pre-mRNA splicing to developmental cell fate decisions

Cyclin-dependent kinases (CDKs) and cyclins are integral to regulating cell cycle progression. However, many cyclins 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. In this study, we investigated the roles of CYL-1 during the development of Caenorhabditis elegans . Our findings revealed that CYL-1 is ubiquitously expressed in cell nuclei throughout development. By performing co-immunoprecipitation 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 with the highly conserved protein EELO-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 and RNA-seq analyses demonstrated that CYL-1 plays a crucial role in transcriptional initiation and elongation as well as pre-mRNA splicing. Furthermore, using a cell fate marker, we demonstrated that CDK-11.1, CDK-11.2, and EELO-1 are also involved in regulating cell fate specification. Collectively, our findings establish that CYL-1 forms a complex with CDK-11.1, CDK-11.2, and EELO-1 in orchestrating mRNA biogenesis, while CDK-11.1, CDK-11.2, and EELO-1 are involved in regulating cell fate determination during development. The results not only enhance our understanding of the multifaceted roles of CYL-1 but also demonstrate a differential role in governing developmental processes between CYL-1 and its interactors.