Due to their intrinsic thermodynamic properties, RNA can misfold easily in cells. One way to mitigate RNA misfolding is through the actions of RNA chaperones, which bind and unwind structured RNA molecules and thereby offer opportunities for these misfolded species to refold properly. Such rescue activity has implications for the fitness effects of individual mutations - at least mutations that compromise RNA folding or structure might be buffered by RNA chaperones. However, little is known about the rules governing such mutation buffering. Here, we describe how a model RNA chaperone, the DEAD-box RNA helicase CYT-19, affects the fitness effects of mutations in a model structured RNA, the Tetrahymena group I intron, whose self-splicing activity is dependent on its structure. The goal was to comprehensively catalogue mutational effects on this self-splicing intron in the absence and presence of CYT-19. Conclusions: To date, this work has yielded considerable information about the mutational effects on the Tetrahymena group I intron. My results highlighted the overall complexities in delineating such mutational effects on a model RNA. More importantly, understanding the in vivo mutational effects on a model RNA will have considerable implications for understanding the robustness in RNA folding. Through this project, two-way transfer of knowledge and skills has been achieved.