RESUMO
Queuosine (Q) is a hypermodified RNA nucleoside that is found in tRNAHis , tRNAAsn , tRNATyr , and tRNAAsp . It is located at the wobble position of the tRNA anticodon loop, where it can interact with U as well as C bases located at the respective position of the corresponding mRNA codons. In tRNATyr and tRNAAsp of higher eukaryotes, including humans, the Q base is for yet unknown reasons further modified by the addition of a galactose and a mannose sugar, respectively. The reason for this additional modification, and how the sugar modification is orchestrated with Q formation and insertion, is unknown. Here, we report a total synthesis of the hypermodified nucleoside galactosyl-queuosine (galQ). The availability of the compound enabled us to study the absolute levels of the Q-family nucleosides in six different organs of newborn and adult mice, and also in human cytosolic tRNA. Our synthesis now paves the way to a more detailed analysis of the biological function of the Q-nucleoside family.
Assuntos
Galactose/química , Nucleosídeo Q/síntese química , Animais , Cromatografia Líquida de Alta Pressão/métodos , Células HEK293 , Humanos , Espectrometria de Massas/métodos , Camundongos , Nucleosídeo Q/química , Nucleosídeo Q/metabolismo , Distribuição TecidualRESUMO
RNA contains methylated A-base derivatives. A methylation to m6A and then demethylation regulate homeostasis in mRNA. It is assumed that m6A is mainly demethylated by the α-ketoglutarate dependent oxidase ALKBH5. Here we show that ALKBH5 also demethylates the dimethylated adenosine m62A, which is a non-canonical base present in ribosomal RNA.
