Designing RNA sequences that satisfy target tertiary-structure objectives is an important problem in RNA engineering, with broad applications in synthetic biology and therapeutics. Existing 3D RNA design methods have made substantial progress, but they largely treat the target fold as a geometry-only objective. This is incomplete for RNA, whose functional folds are specified not only by tertiary geometry but also by secondary base-pairing topology. We therefore formulate RNA inverse design as a topology-and-geometry co-design problem and propose TANGO, a multi-objective multi-agent reinforcement learning framework for this task. TANGO adopts a staged curriculum: it first learns a topology-aware policy from secondary-structure targets, then transfers this policy to tertiary-structure targets to train a general co-design model, and finally applies frontier-guided fine-tuning to refine target-specific trade-offs among secondary-structure fidelity, tertiary-structure fidelity, and sequence diversity. Experiments show that TANGO generates diverse and novel designs, improving tertiary- and secondary-structure performance by 18.3% and 52.7%, respectively, over the strongest baseline.
RNA molecules often function through multiple experimentally observed conformational states. A central challenge is to capture ensemble diversity without sacrificing structural fidelity: samples may collapse toward averaged representative structures or drift into unsupported conformational regions. We introduce REFLEX (RNA Ensemble generation calibrated by FLEXibility), a sequence-conditioned generator for RNA backbone-frame ensembles based on a heteroscedastic stochastic bridge on SE(3). During training, experimental B-factors calibrate residue-wise bridge widths, exposing each observed conformer through local perturbation neighborhoods with residue-specific scales while keeping constrained regions sharper. A learned flexibility condition guides the bridge-field network to recover target conformer-specific frames from these calibrated noisy states. At inference, REFLEX uses only the input sequence, requiring no MSA-subsampling heuristics. On a multi-conformer RNA benchmark, REFLEX achieves the best precision-recall trade-off for ensemble coverage across evaluation thresholds, while recovery-stress ablations indicate gains in target-frame recovery under stronger perturbations.