Long-read sequencing reveals complex patterns of wraparound transcription in polyomaviruses
Year: 2022
Type: article
Abstract: Polyomaviruses (PyV) are ubiquitous pathogens that can cause devastating human diseases. Due to the small size of their genomes, PyV utilize complex patterns of RNA splicing to maximize their coding capacity. Despite the importance of PyV to human disease, their transcriptome architecture is poorly characterized. Here, we compare short- and long-read RNA sequencing data from eight human and non-human PyV. We provide a detailed transcriptome atlas for BK polyomavirus (BKPyV), an important human pathogen, and the prototype PyV, simian virus 40 (SV40). We identify pervasive wraparound transcription in PyV, wherein transcription runs through the polyA site and circles the genome multiple times. Comparative analyses identify novel, conserved transcripts that increase PyV coding capacity. One of these conserved transcripts encodes superT, a T antigen containing two RB-binding LxCxE motifs. We find that superT-encoding transcripts are abundant in PyV-associated human cancers. Together, we show that comparative transcriptomic approaches can greatly expand known transcript and coding capacity in one of the simplest and most well-studied viral families.
Source: PLoS Pathogens
Institutions: Broad Institute, Harvard University, Dana-Farber Cancer Institute, University of Michigan, Massachusetts General Hospital, Harvard Stem Cell Institute, National Institutes of Health, National Cancer Institute, Center for Cancer Research, U-M Rogel Cancer Center, Brigham and Women's Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,655
Funders: Dana-Farber/Harvard Cancer Center, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cancer Research UK, National Institutes of Health, U.S. Public Health Service, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: Parameters governing infection with BK polyomavirus, Human Cancer Suppressor Functions of Protein Phosphatase 2A, G1864025506, Cellular Targets of the BKPyV miRNA, G3154927976, G3205903500, Specialized post-transcriptional mechanisms of gene expression in quiescence, G6827099630, Role of RNA methylation in chemoresistant cancer cells, G8646478233, Lung Adenocarcinoma: From Genome Alterations to Therapeutic Discovery, Identification of Novel Oncogenic Signaling Pathways using Viral Perturbations
OpenAlex ID: W4220912299