[
International Worm Meeting,
2021]
During development, genes must be expressed at both the correct time and location. C. elegans utilizes two separate biological timing mechanisms to coordinate development during progression from larvae to adult. The heterochronic pathway ensures the correct spatial and temporal execution of developmental events through a network of protein regulators and microRNAs. The molting cycle coordinates the replacement of the old skin with a new one to allow for growth. LIN-42 has a critical role as a transcriptional regulator that links the heterochronic pathway to the molting cycle. While the mechanisms that underlie LIN-42 control of gene expression remains elusive, the general molecular mechanism of its mammalian homolog, PER, and its role in regulating circadian rhythms, is better understood. Similar to PER levels that oscillate with ~24-hour rhythmicity, LIN-42 levels oscillate in rhythm with each molt and the key domains conserved between LIN-42 and PER are essential to the circadian function of PER. Here, we leverage our knowledge of PER function to investigate the biochemical relationship between LIN-42 and KIN-20, a protein homologous to the primary kinase responsible for regulation of PER function and influence on the clock, Casein Kinase 1δ (CK1δ). We show that the C-terminus of LIN-42 contains two highly conserved kinase-binding motifs that interact with mammalian CK1δ, suggesting that the domains that anchor the kinase to PER2/LIN-42 may be utilized in a similar mechanism. We also show that LIN-42 is phosphorylated by CK1δ to a similar degree and within the same timeframe as CK1 phosphorylation of a PER substrate. C. elegans mutant strains containing deletions of conserved regions show drastic changes in the expression pattern of LIN-42 when compared to wild-type. By exploring the roles of LIN-42 and the C. elegans CK1δ homolog, KIN-20, we aim to identify the biochemical links between these evolutionarily divergent timing mechanisms.