EteRNA offers several different types of puzzles: tutorials, challenges, player puzzles, player projects, and labs. Solving puzzles adds to a player's point total.
Tutorials are a set of special puzzles that introduce the general principles of the game. Players start with a partially completed puzzle and are presented with limited options to solve it. Each tutorial illustrates a different aspect of play.
Several hundred challenges are puzzles supplied by the EteRNA developers. These puzzles are based on the secondary structures of natural RNAs. Most challenges have multiple difficulty levels. Higher levels have more demanding constraints, but award more points when they are successfully completed.
Main Article: Puzzle Design
Player puzzles are similar to challenges, but they are created by players. These puzzles vary wildly in their size, difficulty, and theme. Hundreds of player puzzles have been created, and new puzzles are added every day. All player puzzles are worth 100 points.
Main Article: Lab
The target structure for labs often are player puzzles chosen from the pool of lab candidates. They are generally easy to solve; however, the goal of labs is not merely to solve a puzzle, it's to find the best possible solutions.
The simplest way for newcomers to assess the difficulty of puzzles is to check the number of players who have previously solved the puzzle.
The most common strategies for solving puzzles involve boosting, blocking, and the use of GC closing base pairs. Strategies have also been developed to deal with certain tricky shapes, such as zigzags and tight multiloops.