Synopsis:
The study explores the nuclear transport mechanism of the precursor protein VII from an ancient siadenovirus that utilizes multiple nuclear localization signals (NLSs) and pathways for nuclear delivery. It identifies two strong NLSs that are key drivers of this process, interacting with specific importins. Additionally, a weaker NLS and another signal are responsible for targeting of the nucleolus. The study reveals that the import process is different between the frog and human virus counterparts, rely on different pathways, and indicates that adenoviruses have evolved diverse strategies to ensure the nuclear import of pVII proteins. These findings offer insights into the evolutionary aspects of adenovirus interactions with host nuclear transport systems.