Understanding Transfer Learning of RNA Foundation Models on Downstream Tasks

Foundation models (FMs) pretrained on large-scale sequence data have emerged as a promising paradigm for RNA biology, yet the mechanisms underlying their transferability remain unclear. In this work, we conduct a systematic investigation of transfer learning in RNA FMs across diverse structural and functional tasks. Our results demonstrate that frozen representations from pretrained RNA FMs are not universally transferable, and that the hierarchical feature reuse paradigm prevalent in computer vision does not generally extend to RNA FMs. Instead, pretraining primarily benefits downstream tasks by providing a favorable optimization initialization when pretraining and downstream objectives are well aligned, which accelerates convergence toward flatter minima associated with improved generalization. Overall, our findings characterize pretraining as an optimization prior whose effectiveness is governed by task alignment and model capacity, offering principled guidance for future RNA FMs.