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Identification of RNAs Engaged in Direct RNA-RNA Interaction with a Long Non-Coding RNA

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Published on: July 9, 2021

Non-coding small RNAs buffer protein interactions to prevent oncogenic aggregation: structural dampening of aberrant

Masanobu Chinami¹

¹Cancer Research Division, BFSR Institute, Fukuoka, Japan.

|January 28, 2026

Abstract:

Non-coding RNAs (ncRNAs) modulate protein-protein interactions (PPIs) by shaping the structural context in which binding occurs, rather than acting as direct inhibitors or enhancers. Using an integrative framework combining catRAPID RNA-protein interaction prediction and AlphaFold3-based structural modelling, we analysed RNA-dependent modulation of interaction states across physiological and oncogenic protein complexes. At the network level, physiological PPIs exhibit high shared ncRNA buffering capacity, whereas oncogenic interactions are characterized by reduced or absent RNA overlap. AlphaFold3 modelling of mutant IDH1/2 complexes illustrates how loss of RNA buffering permits excessive stabilization of enzyme-associated interfaces, reflected by directional changes in buried surface area (ΔBSA) and contact heterogeneity.

Keywords:

AlphaFold3 Non-coding RNA Rb1–HPV16-E7 and Kras–Raf1 aggregation catRAPID p53-MDM2 protein–protein interactions structural buffering

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lncRNA - Long Non-coding RNAs

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lncRNA - Long Non-coding RNAs

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