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Ian Seim1,2, Vita Zhang1, Ameya P Jalihal1

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Synonymous mutations in messenger RNA (mRNA) can control its structure and function. This reveals a hidden physical code within the genetic code, impacting cellular structures.

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Area of Science:

  • Molecular Biology
  • Biophysics
  • Genetics

Background:

  • The genetic code's degeneracy, where multiple codons encode single amino acids, is well-established.
  • Synonymous mutations are known to influence protein translation and folding.
  • The impact of synonymous mutations on RNA structure and function is often overlooked.

Purpose of the Study:

  • To investigate the role of synonymous mutations in controlling mRNA structure and function.
  • To uncover a potential physical code layered within the genetic code.
  • To understand how mRNA conformational heterogeneity influences cellular structures.

Main Methods:

  • Development of a genetic algorithm to introduce synonymous mutations into mRNA sequences.
  • Analysis of mRNA structural diversity and conformational heterogeneity.
  • Investigation of the physical properties and functional outputs of RNA-protein complexes and biomolecular condensates.

Main Results:

  • Synonymous mutations can be used to control the structural diversity of mRNA.
  • mRNA conformational heterogeneity plays a crucial role in directing the physical properties of RNA-protein complexes and biomolecular condensates.
  • A physical code, layered within the genetic code, governs mRNA behavior.

Conclusions:

  • mRNA conformational heterogeneity is as important as protein structure/disorder in biomolecular condensates.
  • The genetic code's degeneracy offers a mechanism for controlling RNA structure and function.
  • This understanding enables the engineering of cellular structures with tailored material and responsive properties.