The Human Adenovirus 2 Transcriptome: an Amazing Complexity of Alternatively Spliced mRNAs
Amanda Westergren Jakobsson, Bo Segerman, Ola Wallerman, Sara Bergström Lind, Hongxing Zhao, Carl‐Johan Rubin, Ulf Pettersson, Göran Akusjärvi
Abstract
Work in the adenovirus system led to the groundbreaking discovery of RNA splicing and alternative RNA splicing in 1977. These mechanisms are essential in mammalian evolution by increasing the coding capacity of a genome. Here, we have used a long-read sequencing technology to characterize the complexity of human adenovirus pre-mRNA splicing in detail. It is mindboggling that the viral genome, which only houses around 36,000 bp, not being much larger than a single cellular gene, generates more than 900 alternatively spliced mRNAs. Recently, adenoviruses have been used as the backbone in several promising SARS-CoV-2 vaccines. Further improvement of adenovirus-based vaccines demands that the virus can be tamed into an innocent carrier of foreign genes. This requires a full understanding of the components that govern adenovirus replication and gene expression.