Hypertrophic cardiomyopathy MYH7 mutation R723G alters mRNA secondary structure

Area of Science:

• Molecular Biology
• Genetics
• Cardiovascular Diseases

Background:

• A specific point mutation (R723G) in the MYH7 gene is linked to hypertrophic cardiomyopathy (HCM).
• Patients with this mutation display an allelic imbalance in MYH7 gene expression, with the mutated allele being more abundant.
• The underlying mechanisms for this mRNA allelic imbalance are not well understood.

Purpose of the Study:

• To investigate whether the R723G mutation alters the secondary structure of MYH7 mRNA.
• To explore if altered mRNA secondary structure could explain the observed allelic imbalance in HCM patients.

Main Methods:

• Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) was used to experimentally assess mRNA secondary structure.
• Bioinformatic predictions of RNA secondary structures were employed for comparison.

Main Results:

• Significant differences in SHAPE reactivity were observed between wild-type and MYH7 R723G mutant RNA.
• Experimental findings were consistent with bioinformatically predicted structural alterations.
• This provides the first experimental evidence linking the HCM point mutation to changes in mRNA secondary structure.

Conclusions:

• The R723G mutation in MYH7 induces alterations in mRNA secondary structure.
• These structural changes are hypothesized to increase the mRNA's stability or lifetime.
• Prolonged MYH7 R723G mRNA lifetime is proposed as a mechanism for the observed allelic imbalance in HCM patients.