Casein Kinase 1δ Stabilizes Mature Axons by Inhibiting Transcription Termination of Ankyrin

Abstract

After axon outgrowth and synapse formation, the nervous system transitions to a stable architecture. In C. elegans, this transition is marked by the appearance of casein kinase 1δ (CK1δ) in the nucleus. In CK1δ mutants, neurons continue to sprout growth cones into adulthood, leading to a highly ramified nervous system. Nervous system architecture in these mutants is completely restored by suppressor mutations in ten genes involved in transcription termination. CK1δ prevents termination by phosphorylating and inhibiting SSUP-72. SSUP-72 would normally remodel the C-terminal domain of RNA polymerase in anticipation of termination. The antitermination activity of CK1δ establishes the mature state of a neuron by promoting the expression of the long isoform of a single gene, the cytoskeleton protein Ankyrin.

Keywords: Ankyrin; Paf1C; Ssu72; alternative polyA sites; casein kinase 1δ; gene loops; kin-20; nervous system maturation; transcription termination; unc-44.