Thermal adaptation of mRNA secondary structure: stability versus lability

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Biophysics

Background:

• Macromolecular function relies on reversible structural changes (conformations).
• Marginal stability of macromolecule conformations is sensitive to temperature, affecting function.
• Proteins evolve to maintain optimal stability across temperatures, but mRNA adaptations are less understood.

Purpose of the Study:

• To investigate temperature adaptation in messenger RNA (mRNA) secondary structures.
• To determine the relationship between mRNA folding stability and environmental adaptation temperature.
• To explore the role of sequence composition in mRNA thermal adaptation.

Main Methods:

• In silico analysis of mRNA secondary structures.
• Estimation of free energy of folding (ΔG_fold) for orthologous mRNAs.
• Comparative analysis of 25 cytosolic malate dehydrogenase mRNAs from marine mollusks across a 60°C temperature range.

Main Results:

• mRNA folding free energy (ΔG_fold) is significantly correlated with adaptation temperature.
• ΔG_fold values are negative and increase in magnitude with higher adaptation temperatures.
• Synonymous guanine + cytosine substitutions increase with rising adaptation temperatures, enhancing mRNA stability.

Conclusions:

• mRNA secondary structure stability is a key factor in thermal adaptation.
• Increased GC content in mRNA sequences is a primary mechanism for adapting to higher temperatures.
• Findings offer insights into the interplay between mRNA sequence evolution and protein adaptation.