[Sequence- and Timing- Dependent Manipulation of RNA Methylation]

Area of Science:

• Molecular Biology
• Epigenetics
• RNA Biology

Background:

• The epitranscriptome, including N6-methyladenosine (m6A) modifications, regulates gene expression and is implicated in diseases.
• Current methods like enzymatic knockdown lack specificity, limiting the understanding of individual m6A roles.
• Selective regulation of RNA methylation states by RNA sequences is crucial for elucidating epitranscriptome functions.

Purpose of the Study:

• To develop molecular tools for sequence-selective and temporal control of RNA methylation.
• To investigate the function of specific RNA methylation sites in biological processes and diseases.

Main Methods:

• Engineered RNA-binding proteins to create sequence-specific RNA demethylases and methylases.
• Demonstrated artificial protein ability to regulate adenosine methylation near target RNA sequences.
• Developing systems for external stimulus-dependent switching of methylation and demethylation activities.

Main Results:

• Successfully created artificial proteins that selectively control RNA methylation states based on RNA sequence.
• Showcased the ability to target and modify specific adenosine methylation sites.
• Initiated development of externally controllable epitranscriptome regulation systems.

Conclusions:

• Developed innovative molecular tools for precise, sequence-specific epitranscriptome modulation.
• These tools enable detailed investigation into the functional roles of specific RNA methylation marks.
• Future developments aim for externally controlled, dynamic regulation of RNA methylation patterns.