Cell-cycle-driven noncanonical ubiquitination of METTL14 orchestrates RNA methylation.

Cell-cycle-dependent K27-linked ubiquitination of METTL14 by RLIM regulates RNA methylation without affecting protein stability.

• Why it matters: Understanding how mRNA methylation is precisely timed during the cell cycle is crucial for insights into gene regulation and disease processes, yet the mechanisms are unclear.
• What they did: The study used cellular and animal models, including human cells and knockout mice, to investigate how RLIM-mediated K27-Ub modification of METTL14 varies with cell cycle phases, involving CDK1/cyclin B1 phosphorylation.
• The result: Findings reveal a periodic, cell-cycle-coupled regulation of m6A methylation through a novel ubiquitination pathway, highlighting a new layer of epitranscriptomic control with implications for disease states like leukemia.