Nucleoside analogs in the study of the epitranscriptome

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Over 150 unique RNA modifications are known, collectively termed the epitranscriptome.
• These modifications, including nonstandard nucleotides in messenger RNA, can significantly alter transcript function.
• Chemically modified nucleoside analogs are crucial tools for investigating these epitranscriptomic marks.

Purpose of the Study:

• To review methods for synthesizing RNA containing chemically modified nucleoside analogs.
• To highlight the role of these analogs in studying the epitranscriptome.
• To provide examples of recent applications in epitranscriptomic research.

Main Methods:

• Discussion of three primary methods for incorporating nucleoside analogs into RNA.
• Metabolic labeling of RNA.
• Enzymatic synthesis using modified nucleotide triphosphates.
• Chemical synthesis via phosphoramidite chemistry.

Main Results:

• Nucleoside analogs with introduced chemical features offer unique structures for detection and quantification.
• Each synthesis method has specific applications and advantages for epitranscriptome research.
• Recent examples demonstrate the utility of these analogs in advancing epitranscriptomic studies.

Conclusions:

• The synthesis and application of chemically modified nucleoside analogs are essential for advancing epitranscriptome research.
• Understanding these incorporation methods facilitates the study of RNA modifications and their functional impact.
• This review provides a foundation for researchers utilizing nucleoside analogs in epitranscriptomics.