The circadian dynamics of small nucleolar RNA in the mouse liver.

The circadian regulation of gene expression allows plants and animals to anticipate predictable environmental changes. While the influence of the circadian clock has recently been shown to extend to ribosome biogenesis, the dynamics and regulation of the many small nucleolar RNA that are required in pre-ribosomal RNA folding and modification are unknown. Using a novel computational method, we show that 18S and 28S pre-rRNA are subject to circadian regulation in a nuclear RNA sequencing time course. A population of snoRNA with circadian expression is identified that is functionally associated with rRNA modification. More generally, we find the abundance of snoRNA known to modify 18S and 28S to be inversely correlated with the abundance of their target. Cyclic patterns in the expression of a number of snoRNA indicate a coordination with rRNA maturation, potentially through an upregulation in their biogenesis, or their release from mature rRNA at the end of the previous cycle of rRNA maturation, in antiphase with the diurnal peak in pre-rRNA. Few cyclic snoRNA have cyclic host genes, indicating the action of regulatory mechanisms in addition to transcriptional activation of the host gene. For highly expressed independently transcribed snoRNA, we find a characteristic RNA polymerase II and H3K4me3 signature that correlates with mean snoRNA expression over the day.