Published on Jan. 1, 2019 in Nat Chem Biol volume 15, 1.
PubMed ID: 30531910
N-Methyladenosine (mA) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA mA modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of mA methyltransferases for rRNAs and the function of rRNA mA modifications are unknown. Here we report a new mA methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates mA4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA mA modification in translation and in tumor biology.