RNAmodifying

RNA modification refers to chemical changes made to RNA nucleotides after transcription. Collectively termed the epitranscriptome, these modifications regulate RNA stability, localization, splicing, translation, and interactions with proteins and other RNAs across coding and noncoding RNAs.

Writers install modifications, erasers remove them, and readers interpret them to influence outcomes. In many eukaryotes, N6-methyladenosine (m6A) is the most abundant internal mark on mRNA, installed by the METTL3–METTL14 complex with regulatory partner WTAP; demethylases such as FTO and ALKBH5 reverse the mark; readers like YTHDF1–3 and YTHDC1 mediate effects on stability, splicing, export, or translation.

Other prevalent modifications include 5-methylcytosine (m5C), 2'-O-methylation, pseudouridine (Psi), and adenosine-to-inosine (A-to-I) editing by ADAR enzymes. These marks influence RNA structure, decoding, and function, and are common in rRNA and tRNA as well as mRNA and regulatory RNAs.

Detection and study rely on antibody-based methods (MeRIP/m6A-seq), crosslinking-based approaches (miCLIP), and high-resolution mass spectrometry; newer strategies include direct RNA sequencing with nanopores. Functional work on writers, erasers, and readers links RNA modification to development, stress responses, and disease.

The field continues to identify new modification types and readers, revealing complex layers of post-transcriptional regulation.