Epitranscriptomics

Epitranscriptomics is the study of chemical modifications to RNA that regulate its fate and function without changing the underlying sequence. Modifications occur on messenger RNA, transfer RNA, ribosomal RNA, and noncoding RNAs and can influence splicing, export, stability, translation, and localization. The field recognizes more than a hundred RNA modifications, with N6-methyladenosine (m6A) as the most prevalent internal mark in eukaryotic mRNA. Other commonly studied modifications include 5-methylcytosine (m5C), N1-methyladenosine (m1A), pseudouridine (Ψ), and various 2'-O-methylations.

The effects of RNA modifications are dynamic and context dependent. Enzymes that add marks (writers, such as the METTL3–METTL14 complex for m6A; NSUN-family enzymes for m5C) can be countered by erasers (e.g., FTO, ALKBH5), while reader proteins (such as YTH domain readers) interpret the marks to influence downstream RNAs' fate.

Functional impacts span mRNA stability and translation, splicing, localization, and response to stress. Epitranscriptomic marks participate in development, differentiation, circadian regulation, and disease processes, including cancer and neurological disorders.

Detection and analysis rely on antibody-based approaches like MeRIP-Seq for transcriptome-wide maps, with newer methods (miCLIP, m6A-CLIP) providing higher resolution. Direct RNA sequencing on nanopore platforms and chemical sequencing methods enable base-level detection, while mass spectrometry yields global modification levels.

Challenges include mapping accuracy, functional attribution, and context-specific effects across tissues and species. Epitranscriptomics thus adds a layer of regulatory complexity to gene expression by revealing reversible RNA chemistry as a post-transcriptional control mechanism.