2'-O-methylation (Nm) in RNA: progress, challenges, and future directions

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• RNA 2 -O-methylation (Nm) is a prevalent modification in noncoding RNAs (rRNA, tRNA, snRNA) and mRNA 5 -caps.
• Internal mRNA Nm sites are increasingly reported, but their detection and validity are debated.
• Nm modifications influence critical cellular processes like translation and splicing, and modulate immune responses.

Approach:

• Review of high-throughput methods for transcriptome-wide Nm detection.
• Discussion of limitations in current methodologies, particularly for internal mRNA sites.
• Synthesis of existing knowledge on Nm's biological roles and disease associations.

Key Points:

• Nm affects RNA function, including translation and splicing.
• Nm modifications in mRNA can prevent innate immune activation.
• Nm is implicated in various diseases, such as cancer and neurological disorders.

Conclusions:

• Significant challenges persist in characterizing Nm distribution, regulation, and functional impact.
• Further research is needed to validate internal mRNA Nm sites and elucidate their roles.
• Understanding Nm's disease relevance is crucial for developing therapeutic strategies.