Lack of evidence for transcription-to-RNA maturation lags across G1-to-G2-phase boundary in fibroblasts.

Cell-cycle dynamics of gene expression are fundamental to life, yet their mechanistic basis remains unclear. A prevailing model, derived from cancer cells, posits that RNAs transcribed in one cell-cycle phase peak in abundance in subsequent phases, suggesting temporal segregation of transcriptional regulation and RNA maturation during the cell cycle. However, whether such extensive transcription-to-maturation lags occur in normal cells remains unclear. Here, we report a lack of evidence for systematic transcription-to-maturation lags extending across the G1-to-G2-phase boundary in normal fibroblasts. Using FUCCI cell-cycle reporters coupled with RNA-seq and GRO-seq, we defined the cell-cycle dynamics of nascent transcription and mature RNA abundance in BJ-5ta human fibroblasts. Transcription and mature RNA accumulation were strongly temporally concordant. Genes with peak transcription in G1, early S, or late S/G2/M showed peak mature RNA abundance in the corresponding phases, without extensive lags. Minor lags within the G1 phase were detected, confirming the sensitivity of our approach. Thus, our data do not support the generality of the prevailing model of extensive transcription-to-accumulation lags in normal human cells.