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

K27-linked ubiquitination of METTL14 by RLIM during the cell cycle regulates mRNA m6A levels independently of protein stability.

• Why it matters: Understanding how mRNA methylation is precisely controlled during the cell cycle is crucial, as its dysregulation is linked to diseases like leukemia.
• What they did: The study used transcriptome analysis, protein modification assays, and models including human cells, knockout mice, and leukemia patients to investigate the regulation of METTL14 by RLIM and CDK1/cyclin B1.
• The result: Findings reveal that K27-Ub on METTL14 oscillates with the cell cycle, mediated by RLIM phosphorylation and degradation, highlighting a cell-cycle-dependent epitranscriptomic regulation pathway.