MiR-10a* up-regulates coxsackievirus B3 biosynthesis by targeting the 3D-coding sequence

Area of Science:

• Molecular Biology
• Virology
• Gene Regulation

Background:

• MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression.
• Most miRNAs suppress gene expression, while their star strands (miRNA*) are usually degraded.
• Group B coxsackieviruses (CVB) cause viral myocarditis; miR-342-5p was previously shown to suppress CVB.

Purpose of the Study:

• To investigate the role of miR-10a duplex in CVB3 biosynthesis.
• To identify whether the miRNA* strand of miR-10a positively regulates gene expression.
• To explore the potential involvement of miR-10a* in CVB3 cardiac pathogenesis.

Main Methods:

• Investigated the effect of miR-10a duplex on CVB3 biosynthesis.
• Utilized site-directed mutagenesis to identify the target sequence of miR-10a* in the CVB3 genome.
• Detected miR-10a* expression in cardiac tissues of infected mice.

Main Results:

• The miR-10a duplex significantly up-regulated CVB3 biosynthesis.
• The star strand, miR-10a*, was identified as the molecule augmenting CVB3 biosynthesis.
• The target site for miR-10a* was mapped to the nt6818-nt6941 region of the CVB3 3D-coding sequence.
• miR-10a* was detected in the cardiac tissues of infected mice.

Conclusions:

• This study demonstrates for the first time that a miRNA* can positively modulate gene expression.
• miR-10a* augments CVB3 biosynthesis by targeting the viral 3D-coding region.
• miR-10a* may play a role in the pathogenesis of CVB3-induced cardiac infection and disease.