# CrossLLM-Mamba: Multimodal State Space Fusion of LLMs for RNA Interaction Prediction

arXiv: https://arxiv.org/abs/2602.22236 · HTML: https://mlsanity.com/paper/2602.22236/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Core SSM architectures for language, one of 10 directions in State-space sequence models (S4, Mamba).
- Builds on 7 of its 27 references that are in the map.
- First posted on arXiv 23 Feb 2026.

## Placed in

- State-space sequence models (S4, Mamba) / [Core SSM architectures for language](https://mlsanity.com/ssm/core-ssm-architectures-for-language/)

## Builds on (most cited first, 7 of 7)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [ViLBERT: Pretraining Task-Agnostic Visiolinguistic Representations for Vision-and-Language Tasks](https://mlsanity.com/paper/1908.02265/) (2019)
- [Tensor Fusion Network for Multimodal Sentiment Analysis](https://mlsanity.com/paper/1707.07250/) (2017)
- [Gated Multimodal Units for Information Fusion](https://mlsanity.com/paper/1702.01992/) (2017)
- [Multimodal Compact Bilinear Pooling for Visual Question Answering and Visual Grounding](https://mlsanity.com/paper/1606.01847/) (2016)
- [Caduceus: Bi-Directional Equivariant Long-Range DNA Sequence Modeling](https://mlsanity.com/paper/2403.03234/) (2024)
- [RiNALMo: General-Purpose RNA Language Models Can Generalize Well on Structure Prediction Tasks](https://mlsanity.com/paper/2403.00043/) (2024)

## Abstract (arXiv)

Accurate prediction of RNA-associated interactions is essential for understanding cellular regulation and advancing drug discovery. While Biological Large Language Models (BioLLMs) such as ESM-2 and RiNALMo provide powerful sequence representations, existing methods rely on static fusion strategies that fail to capture the dynamic, context-dependent nature of molecular binding. We introduce CrossLLM-Mamba, a novel framework that reformulates interaction prediction as a state-space alignment problem. By leveraging bidirectional Mamba encoders, our approach enables deep ``crosstalk'' between modality-specific embeddings through hidden state propagation, modeling interactions as dynamic sequence transitions rather than static feature overlaps. The framework maintains linear computational complexity, making it scalable to high-dimensional BioLLM embeddings. We further incorporate Gaussian noise injection and Focal Loss to enhance robustness against hard-negative samples. Comprehensive experiments across three interaction categories, RNA-protein, RNA-small molecule, and RNA-RNA demonstrate that CrossLLM-Mamba achieves state-of-the-art performance. On the RPI1460 benchmark, our model attains an MCC of 0.892, surpassing the previous best by 5.2%. For binding affinity prediction, we achieve Pearson correlations exceeding 0.95 on riboswitch and repeat RNA subtypes. These results establish state-space modeling as a powerful paradigm for multi-modal biological interaction prediction.