Proteostasis is essential for normal cellular function, with proteins containing intrinsically disordered regions playing a central role in signalling and regulation, while being prone to forming toxic aggregates associated with neurodegenerative diseases. The recently described interstasis mechanism shows that GA-rich multivalent mRNAs regulate the levels of intrinsically disordered proteins through sequestration in nuclear biomolecular condensates. In this master's thesis, we investigate whether interstasis-like principles extend to other types of multivalency and whether multivalency represents a general organisational principle for proteostasis regulation at the transcriptome level. We developed a comprehensive computational approach to identify multivalent regions in the CDS, 3′UTR, and introns of human mRNAs and integrated them with multilayered structural and functional data. At the transcriptome-wide level, we demonstrated that multivalent regions form position-specific clusters and that their patterns in CDS statistically correlate with patterns in non-coding regions, supporting the existence of a coordinated RNA regulatory language. We classified groups of multivalent regions based on sets of structural and functional features and identified candidates potentially linked to proteostasis regulation and biomolecular condensates. Based on the results, we conclude that RNA multivalency is an organised and functionally significant feature that extends the interstasis concept to a broader spectrum of motifs and contributes to fine-tuned homeostasis regulation via a complex RNA regulatory language.
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