RRC ID 76160
Author Dix TC, Haussmann IU, Brivio S, Nallasivan MP, HadzHiev Y, Müller F, Müller B, Pettitt J, Soller M.
Title CMTr mediated 2'-O-ribose methylation status of cap-adjacent nucleotides across animals.
Journal RNA
Abstract Cap methyltransferases (CMTrs) O methylate the 2' position of the ribose (cOMe) of cap-adjacent nucleotides of animal, protist, and viral mRNAs. Animals generally have two CMTrs, whereas trypanosomes have three, and many viruses encode one in their genome. In the splice leader of mRNAs in trypanosomes, the first four nucleotides contain cOMe, but little is known about the status of cOMe in animals. Here, we show that cOMe is prominently present on the first two cap-adjacent nucleotides with species- and tissue-specific variations in Caenorhabditis elegans, honeybees, zebrafish, mouse, and human cell lines. In contrast, Drosophila contains cOMe primarily on the first cap-adjacent nucleotide. De novo RoseTTA modeling of CMTrs reveals close similarities of the overall structure and near identity for the catalytic tetrad, and for cap and cofactor binding for human, Drosophila and C. elegans CMTrs. Although viral CMTrs maintain the overall structure and catalytic tetrad, they have diverged in cap and cofactor binding. Consistent with the structural similarity, both CMTrs from Drosophila and humans methylate the first cap-adjacent nucleotide of an AGU consensus start. Because the second nucleotide is also methylated upon heat stress in Drosophila, these findings argue for regulated cOMe important for gene expression regulation.
Volume 28(10)
Pages 1377-1390
Published 2022-10-1
DOI 10.1261/rna.079317.122
PII rna.079317.122
PMID 35970556
PMC PMC9479742
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Drosophila / genetics Drosophila / metabolism Humans Methylation Methyltransferases / metabolism Mice Nucleotides / genetics Nucleotides / metabolism RNA Caps* / chemistry RNA, Messenger / genetics Ribose* / metabolism Zebrafish / genetics
C.elegans tm4453