N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation

International audienceN6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 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 m6A modification in translation and in tumor biology

m(6)A mRNA Methylation in the Mammalian Brain: Distribution, Function and Implications for Brain Functions

RNA is abundantly modified by a range of covalent modifications, collectively termed the epitranscriptome. Of these modifications, N-6-methyladenosine (m(6)A) is the most prevalent internal chemical tag in eukaryotic mRNA. Being cotranscriptionally deposited, it regulates almost all aspects of mRNA's lifetime including maturation into mRNA, stability, distribution and protein translation. While m(6)A is likely present in all developing and adult mammalian tissues, here we highlight its distribution and reported functions in the mammalian brain. Additionally, we describe its potential to act as an encoding mechanism for activity- and experience-dependent adaptation and memory-formation. Such alterations may be positive when adjusting to outer challenges or negative when involved in maladaptive processes of the brain such as in the development of psychopathologies. Consequently, studying this layer of gene expression control in the brain, alongside posttranslational regulation of proteins and epigenetics may inform us as to the molecular mechanisms underlying normal and pathological behaviors. Unfortunately, measuring m(6)A levels, patterns and especially dynamics still poses a major technological challenge especially in such a complicated organ as the brain