Ribosomal RNAs (rRNAs) function as scaffolds and ribozymes in ribosomes, and their function and stability is regulated by nucleotide modifications, including RNA base methylation. Despite this modification being well conserved and thought to expand the structural repertoire of RNA, its role in ribosome function remains poorly understood. In their article on page , Yuka Nakajima and colleagues investigate the role of nucleolar protein nucleomethylin (NML), which regulates intracellular energy consumption by limiting rRNA transcription under glucose deprivation, in HeLa cells. The authors show here that NML methylates adenosine 1310 (A1310) in human 28S rRNA, and that this is important for the formation of 60S ribosomal subunits. Interestingly, depletion of NML leads to an increase in the amount of ribosomal protein L11 (RPL11) in the ribosome-free fraction and also results in enhanced interaction of the protein with MDM2, the negative regulator of p53. Accordingly, p53 is activated upon NML depletion as demonstrated by a suppression of proliferation and cell cycle arrest in NML-knockdown cells. Taken together, the data presented here establish a link between ribosome biogenesis and cell proliferation through a mechanism that involves rRNA base methylation, and free RPL11 and p53. Future directions include exploring the possibility of a role for rRNA modifications in cancer development.
