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Folding Stability and Self‐Association of a Triplet‐Repeat (CAG) 20 RNA Hairpin in Cytomimetic Media
Author(s) -
Hautke Alexander Christoph,
Ebbinghaus Simon
Publication year - 2021
Publication title -
chemsystemschem
Language(s) - English
Resource type - Journals
ISSN - 2570-4206
DOI - 10.1002/syst.202000052
Subject(s) - trinucleotide repeat expansion , rna , folding (dsp implementation) , in vitro , biology , computational biology , biophysics , microbiology and biotechnology , protein folding , rna binding protein , chemistry , genetics , allele , gene , electrical engineering , engineering
RNA molecules with trinucleotide repeat expansions are involved in the pathology of various neurodegenerative diseases, such as Huntington's disease. A central research objective is to understand how trinucleotide repeat RNAs fold and function in disease progression. Studies that investigate the sequence structure, stability and self‐assembly of such RNAs mainly focused on in vitro methods in dilute aqueous solution. Functional studies in cells reveal further aspects of transport, protein association or assembly in phase separated compartments. Our study aims to understand governing factors for folding stability of trinucleotide repeats on the cellular level by assessing the influence of key components of the cellular medium in vitro . We investigate (CAG) 20 RNA in complex and cytomimetic media using Fast Relaxation Imaging. Using distinct cosolutes we analyze the different enthalpic and entropic contributions that determine folding stability. We find a remarkable destabilization and aggregation of the RNA in cellular lysate that can be attributed to specific and non‐specific interactions with the unfolded state.