An RNA-centric atlas of human cell cycle regulation

The human cell cycle is regulated by intricate networks of proteins, but the role of RNA in this process has been largely overlooked. In this study, researchers have created a comprehensive RNA-centric atlas of human cell cycle control. They analyzed normal diploid cells synchronized using palbociclib, examining long non-coding RNAs (lncRNAs), transposable elements (TEs), alternative splicing (AS), and RNA-binding proteins (RBPs).

The researchers identified 104 lncRNAs that are regulated during the cell cycle. They further validated the function of lncRNA ENSG00000230615, finding that altering its expression disrupts cell cycle progression and downregulates a neighboring gene called KLF17. Across the entire transcriptome, the study found that 297 TEs show differential expression patterns during the cell cycle, with Alu elements being particularly upregulated during the G1-to-S transition.

Additionally, the researchers discovered that changes in cell cycle-dependant alternative splicing affect 598 genes, with the largest shift in alternative splice site usage occurring at the G1-to-S transition. Notably, proteins involved in cytokinesis, the process of cell division, also function as non-canonical RBPs, regulating RNA stability in an unexpected manner.

Overall, this RNA-centric atlas provides a comprehensive resource on the role of RNA in cell cycle control, shedding light on a previously underappreciated layer of regulation within the cell.