Methylases articles from across Nature Portfolio

Here, the authors use cryo-EM and machine-learning-based tools to analyze structurally heterogeneous ribosome assembly intermediates. They uncover a new proofreading function of the bacterial methyltransferase KsgA, wherein this assembly factor recognizes and drives partial disassembly of translationally incompetent particles, thereby affording these intermediates another opportunity to assemble in an active form.

Ribozymes that use the cellular cofactor S-adenosyl-l-methionine to methylate RNA remained elusive. Now, such a ribozyme is reported by identifying natural sequences that are active in vitro; and crystal structures of the ribozyme with and without the cofactor are determined.

Schuhmacher, Beldar et al. design a super-substrate peptide based on the substrate sequence specificity of the SETD2 protein lysine methyltransferase. SETD2 methylates this super-substrate 290-fold more efficiently than the original H3K36 peptide. This study illustrates that substrate sequence design can improve the activity of protein lysine methyltransferases.

Protein lysine methylation plays important biological roles but its experimental characterization is limited by the lack of suitable mimetics of methylated and unmethylated lysine among the natural amino acids. Here, we summarize the consequent challenges and discuss alternative approaches for biochemical and cellular lysine methylation studies.

The RNA methyltransferase METTL3 catalyzes N⁶-methyladenosine (m⁶A) modification of messenger RNAs (mRNAs). It is overexpressed in many types of cancer, including acute myelogenous leukemia (AML), and promotes cancer cell growth and tumorigenicity. Now, a selective small molecule inhibitor of METTL3 shows significant antileukemic effects in preclinical AML models, highlighting the promise of pharmacological METTL3 inhibition as a new cancer therapy.

Discovery of the first eukaryotic α-N-methyltransferase.