RNA nucleotide methylation: 2021 update.

Area of Science:

• Molecular Biology
• Epigenetics
• RNA Biology

Background:

• Methylation is the most common RNA modification, primarily mediated by methyltransferases (MTases) using S-adenosyl-l-methionine.
• The field of epitranscriptomics has expanded beyond prokaryotes to focus on higher eukaryotes, particularly mammals.
• Historically viewed as irreversible, RNA modifications are now understood to be dynamic and reversible.

Purpose of the Study:

• To review major developments in RNA modification and epitranscriptomics over the past decade.
• To highlight the shift in focus from basic mechanisms to disease relevance and clinical investigations.
• To predict future trends in the study of RNA modifications.

Main Methods:

• Characterization of methyltransferases (MTases) as "writers" of the epitranscriptome.
• Identification of "readers" that bind to methylated RNA and mediate biological effects.
• Discovery of "eraser" enzymes involved in the oxidative removal of methyl groups.
• Development of methylation mapping techniques.

Main Results:

• mRNA methylation re-emerged as a key mechanism in gene regulation.
• MTases are implicated in numerous disease models and clinical investigations.
• The concept of the epitranscriptome encompasses various RNA species and their modifications.
• Reversibility and dynamics, including incomplete methylation leading to modivariants, are now recognized.

Conclusions:

• The field of RNA modification has evolved significantly, emphasizing dynamic processes and disease relevance.
• The "epitranscriptome" concept provides a unifying framework for understanding RNA modifications.
• Future research will likely focus on the interplay of writers, readers, and erasers in health and disease.