Control of Archetype BK Polyomavirus MicroRNA Expression

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• BK polyomavirus (BKPyV) is a common human virus causing disease in transplant patients.
• BKPyV has a circular DNA genome with early, late, and noncoding control regions.
• A BKPyV microRNA (miRNA) regulates viral gene expression and replication, but its expression mechanism is unknown.

Purpose of the Study:

• To investigate the regulatory mechanism of BKPyV miRNA expression.
• To understand how BKPyV optimizes gene expression from its limited genome.

Main Methods:

• Analysis of primary RNA transcripts.
• Identification of splice junctions.
• Sanger sequencing of reverse transcription-PCR products.

Main Results:

• Evidence of primary RNA transcripts that circle the BKPyV genome multiple times.
• Identification of splice junctions from these large transcripts.
• Demonstration that BKPyV miRNA is likely spliced from an intron within these transcripts.

Conclusions:

• BKPyV miRNA is expressed from an intron in greater-than-genome-size primary transcripts.
• This mechanism explains miRNA regulation and viral persistence.
• Viruses can utilize complex RNA processing for gene expression optimization.