The identification and characterization of a selected SAM-dependent methyltransferase ribozyme that is present in natural sequences

RNA methylations contribute to a wide range of cellular functions. Cellular RNAs are usually methylated by protein methyltransferases using S-adenosyl-l-methionine (SAM) as a cofactor. Here we report the in vitro selection of a 33-nucleotide SAM-dependent methyltransferase ribozyme RNA from a randomized sequence. Detection and mapping of the methyl group on the RNA demonstrates site-specific methylation of the N7 position of guanine by SAM. The ribozyme is active over a wide range of pH and temperatures and is robust compared to protein enzymes. The ribozyme structures in the presence and absence of SAM show a dramatic local conformational change associated with cofactor binding. The ribozyme motif was found to be distributed in nature, and candidate sequences were shown to be active in vitro. The discovery of this ribozyme that uses the cofactor SAM to specifically methylate RNA opens up the possibility that methyltransferase ribozymes may contribute to cellular RNA methylation. 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.