RNA Structure: A Modular Reading Sequence for Complete Beginners¶

This reading guide provides a structured path for learning RNA structure from absolute basics to advanced topics. Each module builds on previous knowledge and includes carefully selected papers and resources.

Module 0 — "What is RNA?" (Absolute Beginners)¶

Goal: Basic molecular biology context; what RNA is, how it compares to DNA, types of RNA.

Publications / Resources¶

• Alberts et al., Molecular Biology of the Cell (Intro RNA chapters) — High-level, conceptual introduction to RNA.
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• Sharp, 2009. "The Centrality of RNA." Cell.
  A broad, accessible introduction to why RNA matters.
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• Cech & Steitz, 2014. "The Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones." Cell.
  Gives newcomers a sense of the field's importance without requiring background.
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All Module 0 Papers: Module 0 Papers Folder

Module 1 — Fundamentals of RNA Structure¶

Goal: Nucleotides → base pairing → secondary structure → tertiary interactions.

Publications¶

• Tinoco & Bustamante, 1999. "How RNA Folds." J. Mol. Biol.
  Classic conceptual framework for how RNA structure emerges from sequence.

• Doudna & Cech, 2002. "The Chemical Repertoire of Natural Ribozymes." Nature.
  Shows what RNA can do chemically; very accessible.

• Westhof, 2010. "The Pseudoknot." RNA Biology.
  Gentle intro to a common RNA motif.

Access Papers: Module 1 Papers Folder

Module 2 — RNA Secondary Structure (Modern Overview)¶

Goal: Learn base-pairing rules, folding thermodynamics, and the meaning of "secondary structure."

Publications¶

• Mathews, 2006. "Revealing Secondary Structure." Nature Chemical Biology.
  Good short review.

• Lorenz et al., 2011. "ViennaRNA Package 2.0." NAR.
  Teaches what MFE prediction is and why it's limited.

• Watts et al., 2009. "Architecture and Secondary Structure of the HIV-1 RNA Genome." Nature.
  Shows how experimental methods map real structures.

Access Papers: Module 2 Papers Folder

Module 3 — Experimental RNA Structure Probing¶

Goal: Understand what chemical probing is and how structure is measured experimentally.

Publications¶

• Deigan et al., 2009. "Accurate SHAPE-directed RNA Structure Determination." PNAS.
  The conceptual beginning of modern structure probing.

• Wilkinson, Merino & Weeks, 2006. "RNA SHAPE Chemistry: A Selective 2′-Hydroxyl Acylation …" Nat Protoc.
  Accessible protocol that explains the logic.

• Rouskin et al., 2014. "Genome-wide probing of RNA structure in vivo." Nature.
  Landmark paper introducing in vivo probing.

Access Papers: Module 3 Papers Folder

Module 4 — Mapping RNA Tertiary Interactions¶

Goal: Introduce students to the idea of tertiary contacts and RNA folding landscapes.

Publications¶

• Russell, 2008. "RNA Misfolding and the Trapped Ribosome." Nature Structural & Molecular Biology.
  Clear conceptual introduction to tertiary folding problems.

• Bokinsky et al., 2003. "Single-molecule folding of a ribozyme." Science.
  Great visualization of folding pathways.

• Kladwang et al., 2011. "Two-dimensional chemical mapping of RNA tertiary structure." Nat Chem.
  Modern view of how tertiary contacts can be inferred experimentally.

Access Papers: Module 4 Papers Folder

Module 5 — RNA Motifs and 3D Structure (Beginner-Friendly)¶

Goal: Learn canonical motifs (tetraloops, K-turns, A-minor, etc.) and how 3D structure works.

Publications¶

• Leontis & Westhof, 2001. "Geometric nomenclature and classification of RNA base pairs." RNA.
  A must-read for understanding tertiary interactions.

• Cruz & Westhof, 2009. "The Dynamic Landscapes of RNA Architecture." Cell.
  Very accessible overview of motifs.

• Holbrook, 2008. "Structural principles from large RNAs." Annual Review of Biophysics.

Access Papers: Module 5 Papers Folder

Module 6 — RNA Folding Thermodynamics & Kinetics¶

Goal: Understand forces, energetics, Mg²⁺ dependence, and folding equilibria.

Publications¶

• Woodson, 2010. "Slow RNA Folding as a Stochastic Process." J. Mol. Biol.
  Very intuitive introduction to folding kinetics.

• Thirumalai & Hyeon, 2005. "RNA and RNA-protein Folding: Common Themes." Biochemistry.

• Draper, 2008. "RNA–Mg²⁺ interactions." Curr Opin Struct Biol.
  Beginner-friendly explanation of Mg²⁺ and tertiary stabilization.

Access Papers: Module 6 Papers Folder

Module 7 — RNA Structure in Cellular Context¶

Goal: Understand RNA structure in vivo, RNPs, and functional implications.

Publications¶

• Mortimer, Kidwell & Doudna, 2014. "Insights into RNA Structure and Function from Genome-wide Studies." Nat Rev Genet.

• Rangan et al., 2021. "RNA Structure: Biology, Chemistry, and Methods." Nat Rev Mol Cell Biol.
  Excellent modern review for students.

Access Papers: Module 7 Papers Folder

Module 8 — Modern High-Throughput & Computational Methods¶

Goal: Prepare students for modern RNA structure biology (chemical mapping, AI, large datasets).

Publications¶

• Mustoe et al., 2018. "Pervasive Regulatory Functions of RNA Structure…" Cell.

• Smola et al., 2015. "SHAPE-MaP for genome-wide RNA structure analysis." Nat Protoc.

• Herschlag et al., 2018. "RNA: One Molecule, Many Mysteries." JBC.
  A high-level but very readable overview of modern problems.

Access Papers: Module 8 Papers Folder

Module 9 — Advanced (Optional)¶

Goal: Cutting-edge topics once students have mastered basics.

Publications¶

Machine-learning RNA structure prediction¶

• Townshend et al., 2021. "Geometric deep learning of RNA structure." Science.

RNA thermodynamics databases¶

• Kim et al., 2022. "Updated nearest-neighbor parameters for RNA secondary structure." NAR.

High-throughput RNA tertiary mapping¶

• Yesselman Lab (in prep / published) — qMaPseq, tertiary thermodynamics, etc.

Access Papers: Module 9 Papers Folder

How to Use This Guide¶

For Complete Beginners¶

1. Start with Module 0 - Don't skip this! It provides essential context.
2. Read sequentially - Each module builds on previous knowledge.
3. Take notes - Write down key concepts and questions.
4. Don't rush - Understanding is more important than speed.

For Students with Some Background¶

1. Assess your knowledge - Review Module 0 and 1 to identify gaps.
2. Focus on weak areas - Spend more time on modules covering unfamiliar topics.
3. Skip ahead carefully - Only skip modules if you're confident in the material.

Reading Tips¶

• Read abstracts first - Get a sense of the paper before diving in.
• Focus on figures - They often convey key concepts more clearly than text.
• Read methods - Understanding how experiments work is crucial (see Lab Guide FAQ).
• Discuss with others - Lab meetings and study groups help understanding.

Accessing Papers¶

All papers are organized in folders within this documentation repository. Each module has its own folder containing the relevant PDFs.

Paper Folders¶

• Module 0 Papers - "What is RNA?" (Absolute Beginners)
• Module 1 Papers - Fundamentals of RNA Structure
• Module 2 Papers - RNA Secondary Structure
• Module 3 Papers - Experimental RNA Structure Probing
• Module 4 Papers - Mapping RNA Tertiary Interactions
• Module 5 Papers - RNA Motifs and 3D Structure
• Module 6 Papers - RNA Folding Thermodynamics & Kinetics
• Module 7 Papers - RNA Structure in Cellular Context
• Module 8 Papers - Modern High-Throughput & Computational Methods
• Module 9 Papers - Advanced Topics

Paper Naming Convention¶

Papers in the folders follow this format:

AUTHOR_YEAR_TITLE.pdf

Example:

Deigan_2009_Accurate_SHAPE_directed_RNA_Structure_Determination.pdf

Adding Papers¶

To add papers to the repository: 1. Place PDFs in the appropriate module folder (docs/resources/papers/module-X/) 2. Use the naming convention above 3. Commit and push to the repository

Progress Tracking¶

Recommended Study Schedule¶

• Week 1-2: Module 0 & 1 (Foundations)
• Week 3-4: Module 2 & 3 (Secondary Structure & Probing)
• Week 5-6: Module 4 & 5 (Tertiary Structure & Motifs)
• Week 7-8: Module 6 & 7 (Thermodynamics & Cellular Context)
• Week 9-10: Module 8 & 9 (Modern Methods & Advanced Topics)

Adjust based on your background and available time.

Questions to Consider After Each Module¶

1. What are the key concepts I learned?
2. How does this connect to previous modules?
3. What questions do I still have?
4. What would I like to explore further?

Additional Resources¶

Textbooks¶

• Molecular Biology of the Cell (Alberts et al.) - General molecular biology
• RNA Structure and Function (Pyle) - Comprehensive RNA structure textbook

Online Resources¶

• RNA Structure Database - 3D RNA structures
• ViennaRNA Web Services - RNA folding tools
• RNAcentral - RNA sequence database

Lab Resources¶

• Lab Software Documentation - Tools for RNA analysis
• Protocols - Experimental protocols
• Getting Started Guide - Lab setup and policies

Questions?¶

If you have questions about: - Paper content: Discuss in lab meetings or reach out to lab members - Access issues: Contact lab manager for Google Drive access - Study strategies: Talk to your mentor or PI

Last updated: November 23, 2025