CK1δ and CK1ε are components of human 40S subunit precursors required for cytoplasmic 40S maturation.

Biogenesis of 40S pre-ribosomal subunits requires many trans-acting factors, among them several protein kinases. In this study, we show that the human casein kinase 1 (CK1) isoforms δ and ε are required for cytoplasmic maturation steps of 40S subunit precursors. We show that both CK1δ and CK1ε isoforms are components of pre-40S subunits, on which they phosphorylate the ribosome biogenesis factors ENP1/BYSL and LTV1. Inhibition or co-depletion of CK1δ and CK1ε results in failure to recycle a series of trans-acting factors including ENP1/BYSL, LTV1, RRP12, DIM2/PNO1, RIO2 and NOB1 from pre-40S particles after nuclear export. Furthermore, co-depletion of CK1δ and CK1ε leads to defects in 18S-E pre-rRNA processing. Together, these data demonstrate that CK1δ and CK1ε play a decisive role in triggering late steps of pre-40S maturation that are required for acquisition of functionality of 40S ribosomal subunits in protein translation.