VeloRM: disentangling pre- and post-splicing RNA modification dynamics at single-cell resolution

Area of Science:

• Molecular Biology
• Computational Biology
• Genomics

Background:

• RNA modifications are crucial for RNA function but their dynamics are poorly understood.
• Cellular transitions involve complex regulatory changes, including in RNA modifications.

Purpose of the Study:

• To develop a computational framework (VeloRM) for analyzing RNA modification dynamics at single-cell resolution.
• To differentiate epitranscriptomes before and after RNA splicing.
• To model epitranscriptomic changes and reconstruct cellular trajectories.

Main Methods:

• Development of the VeloRM computational framework.
• Analysis of single-cell RNA modification data (m6A and A-to-I editing).
• Modeling of epitranscriptomic velocities to predict RNA modification states and cellular trajectories.

Main Results:

• VeloRM successfully recapitulates known cell cycle and differentiation trajectories.
• Identification of novel m6A modification sites on prespliced RNAs near splice junctions.
• Demonstration of dynamic m6A patterns with functional implications in splicing regulation.

Conclusions:

• VeloRM provides a powerful tool for studying epitranscriptome dynamics during biological transitions.
• The framework enables unprecedented insights into RNA modification regulation.
• New findings highlight the role of m6A modifications in splicing regulation.