Review toward all RNA structures, concisely.

Area of Science:

• Biochemistry
• Molecular Biology
• Genomics

Background:

• Understanding nucleic acid structure and function is crucial in molecular biology.
• Complex biological systems often require simplified, chemistry-based experimental approaches.
• The work of Don Crothers emphasized direct experimentation for complex biological questions.

Purpose of the Study:

• To review the development of SHAPE-MaP and RING-MaP technologies.
• To highlight the importance of direct, chemistry-based experimental strategies.
• To advocate for a shift towards less inferential "omics" investigations.

Main Methods:

• Development of Selective 2′-Hydroxyl Acylation analyzed by Primer Extension and Mutational Profiling (SHAPE-MaP).
• Development of RNA single-nucleotide Resolution Accessibility and Mutational Profiling (RING-MaP).
• Application of these methods to interrogate RNA structure and function at large scales.

Main Results:

• SHAPE-MaP and RING-MaP technologies enable large-scale interrogation of RNA structure and function.
• Direct, chemistry-based experiments provide profound insights into nucleic acids.
• Focusing on concise experiments aids in understanding complex genomic architectures and transcriptomes.

Conclusions:

• Direct experimental approaches are key to advancing our understanding of biological function.
• SHAPE-MaP and RING-MaP are powerful tools for studying RNA at scale.
• "Omics" investigations can yield more definitive contributions with increased focus on direct experimentation.