ARTEMIS: a method for topology-independent superposition of RNA 3D structures and structure-based sequence alignment

Area of Science:

• Structural biology
• Bioinformatics
• Molecular biology

Background:

• Non-coding RNAs are crucial cellular components, with function dictated by sequence and 3D structure.
• Accurate comparative analysis of RNA 3D structures relies on superposition methods.
• Existing methods struggle with topology-independent superposition, limiting exploration of RNAs with sequence permutations.

Purpose of the Study:

• To develop an advanced computational tool for global RNA 3D structure alignment.
• To improve upon existing methods for both sequentially-ordered and topology-independent RNA superposition.
• To explore conserved structural motifs in non-coding RNAs, particularly those with sequence permutations.

Main Methods:

• Further development of the ARTEM method into a global RNA 3D structure alignment tool named ARTEMIS.
• Evaluation of ARTEMIS against state-of-the-art tools for RNA 3D structure superposition.
• Application of ARTEMIS to identify conserved structural features in various non-coding RNAs.

Main Results:

• ARTEMIS significantly outperforms existing tools in both sequential and topology-independent RNA 3D structure superposition.
• Discovery of a conserved helical packing motif present in diverse non-coding RNAs, irrespective of backbone topology.
• Identification of this motif across multiple ribozymes and riboswitches.

Conclusions:

• ARTEMIS is a powerful new tool for RNA 3D structure analysis and alignment.
• The tool facilitates the exploration of RNA structural motifs, including those with sequence permutations.
• ARTEMIS is expected to advance the understanding of RNA 3D fold landscapes and functional mechanisms.