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Published on: June 7, 2020
UTR-ly unexpected: RNA chaperones tame intrinsically disordered proteins
Miriam Linsenmeier1, James Shorter1
1Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cell
|July 23, 2026
Summary
Cells use the 3' untranslated region (UTR) of mRNA to chaperone proteins during translation. This prevents misfolding of complex proteins by guiding proper folding within cellular condensates.
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Biology
Background:
- Correct protein folding is crucial for cellular function, especially for complex, multidomain proteins.
- The process of protein folding has traditionally been understood through Anfinsen's dogma, focusing on intrinsic properties of the amino acid sequence.
- The role of non-coding regions of mRNA in protein folding remains an area of active investigation.
Purpose of the Study:
- To investigate how cells ensure the correct folding of complex, multidomain proteins.
- To explore the potential role of messenger RNA (mRNA) in the co-translational folding process.
- To understand the mechanism by which intrinsically disordered regions are managed during protein synthesis.
Main Methods:
- Investigated the function of the 3' untranslated region (UTR) of mRNA.
- Examined the co-translational chaperone activity of mRNA.
- Studied the localization of this process within specific cellular structures, described as mesh-like condensates.
Main Results:
- The 3' UTR of an mRNA acts as a co-translational chaperone for the protein it encodes.
- This chaperone activity prevents intrinsically disordered regions from forming inappropriate contacts.
- The folding process is facilitated within specific, mesh-like condensate structures.
Conclusions:
- The 3' UTR of mRNA provides a self-contained mechanism for ensuring correct protein folding.
- This finding challenges traditional views like Anfinsen's dogma by highlighting mRNA's active role in folding.
- The discovered mechanism presents novel therapeutic possibilities for protein-folding-related diseases.
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