The addition of various chemical modifications to RNA introduces an additional layer of complexity to the regulation of gene expression. Among all RNA modifications, N6-methyladenosine (m6A) has earned its status as the most abundant and well-studied post-transcriptional modification in mammalian mRNA. Nevertheless, understanding the role of m6A in shaping the fate of RNA molecules and its influence on gene expression heavily depends on the development and application of detection technologies. Among all m6A detection methods, chemical-based sequencing methods show unique advantages. Our group recently developed an absolute quantification method named GLORI, which employs nitrite and glyoxal to convert adenosine to inosine efficiently. With its potential to emerge as the gold standard for m6A detection, GLORI showcases the promise of nitrite-based approaches. This review provides a comprehensive overview of m6A detection techniques based on deamination or nitrosation, evaluating their strengths and limitations. Furthermore, we offer insights into the future directions of innovative approaches in m6A profiling.
RNA-guided RNA modifications, including pseudouridylation and 2′-O-methylation, are naturally occurring processes that introduce pseudouridines (Ψ) and 2’-O-methylated residues (2’-O−Me) into various types of RNA. This modification is orchestrated by two distinct families of ribonucleoprotein complexes: Box H/ACA RNP and Box C/D RNP. Each complex comprises a unique guide (g)RNA (Box H/ACA gRNA or Box C/D gRNA) and a set of core proteins responsible for pseudouridylation and 2’-O-methylation, respectively. The specificity of these modifications is conferred by base-pairing of Box H/ACA gRNA and Box C/D gRNA with their RNA substrates. Here, we discuss the mechanism and function of RNA-guided pseudouridylation and 2’-O-methylation.
The cover picture shows a cyclic voltammogram and catalytically active intermediates, highlighting the importance of a rationale for innovations in the rapidly evolving field of molecular electrosynthesis. Also, as a product structure, a C7 substituted indole, derived through electrocatalysis, is depicted.