Long-read sequencing reveals complex patterns of wraparound transcription in polyomaviruses

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• Polyomaviruses (PyV) are significant human pathogens with small genomes.
• PyV rely on complex RNA splicing to maximize coding capacity.
• The transcriptome architecture of PyV remains poorly characterized.

Purpose of the Study:

• To create a detailed transcriptome atlas for BK polyomavirus (BKPyV) and simian virus 40 (SV40).
• To compare short- and long-read RNA sequencing data across eight PyV species.
• To identify novel conserved transcripts and understand PyV coding capacity.

Main Methods:

• Comparative analysis of short- and long-read RNA sequencing data.
• Transcriptome sequencing from eight human and non-human polyomaviruses.
• Bioinformatic analysis to identify novel transcripts and transcription patterns.

Main Results:

• Detailed transcriptome atlases for BKPyV and SV40 were generated.
• Pervasive wraparound transcription was identified in PyV, with transcripts circling the genome.
• Novel conserved transcripts, including one encoding superT antigen with two RB-binding motifs, were discovered.
• SuperT-encoding transcripts are abundant in PyV-associated human cancers.

Conclusions:

• Comparative transcriptomics significantly expands the known transcript and coding capacity of polyomaviruses.
• The discovery of superT antigen highlights a conserved mechanism for increasing PyV coding potential.
• This research provides a comprehensive view of the PyV transcriptome, crucial for understanding pathogenesis.