The detection, function, and therapeutic potential of RNA 2'-O-methylation

The RNA modification 2'-O-methylation (Nm) is an essential RNA modification found across nearly all types of RNAs. This review compares Nm detection methods, and examines its biological roles in health and disease. Researchers have recently used Oxford Nanopore direct RNA sequencing and the NanoNm machine learning tool to map thousands of Nm sites at single-base resolution. They found that Nm has regulatory and structural roles, with implications for cancer, neurodegeneration, and viral immune evasion — highlighting its potential as a biomarker and therapeutic target in the future.

Key points:

• Oxford Nanopore technology enabled amplification-free, full-length RNA sequencing and quantitative Nm detection with single-nucleotide precision, overcoming the major limitations of short-read and chemical-based methods

• NanoNm enables de novo, single-base resolution of Nm from Oxford Nanopore direct RNA sequencing data

• Thousands of Nm sites have been identified in human mRNA and rRNA

• Stoichiometric analysis suggests Nm plays a regulatory role in mRNA and a structural role in rRNA

• Nm is enriched near stop codons and linked to mRNA stability, shortened 3'-UTRs, and increased gene expression

• Fibrillarin overexpression increases Nm on cancer-related transcripts, linking Nm to disease-relevant gene regulation

• Studying Nm could reveal novel diagnostic markers and therapeutic strategies for a wide range of diseases in the future