RNAFirstModelle

RNAFirstModelle is a term used in computational and systems biology to describe modeling strategies that foreground RNA features in the construction of predictive models. In these approaches, RNA sequence and structure, rather than protein-centric features, are used as primary drivers of inference about regulatory networks, gene expression, and RNA function. The term is mainly encountered in German-language discussions and in research articles proposing RNA-centric design principles.

Core ideas include prioritizing RNA structure prediction and RNA dynamics, integrating experimental RNA structure probing data (for example SHAPE-Seq, DMS-seq) to constrain models, and modeling RNA interactions with proteins, other RNAs, and small molecules to understand regulatory outcomes such as riboswitch control, RNA localization, and RNA-based therapeutics.

Methodologically, RNAFirstModelle combines computational RNA structure prediction tools (for example RNAfold and other secondary structure prediction methods) with data-driven approaches (machine learning, graph-based models) and, in some cases, coarse-grained molecular simulations. It aims to produce models of cellular processes where RNA elements play central roles.

Applications include studying noncoding RNA function, gene regulatory networks driven by untranslated regions, riboswitch logic, and the design of RNA-targeted therapeutics. Limitations involve incomplete accuracy of RNA structure predictions, context dependence, scarcity of high-resolution structural data, and the challenge of integrating RNA data with other molecular layers.

As a conceptual framework, RNAFirstModelle reflects a shift toward RNA-centric modeling in systems biology, while remaining complementary to protein- and metabolite-centered approaches.