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Viral nucleocapsid proteins (NCs) enwrap the RNA genomes of viruses to form NC–RNA complexes, which act as a template and are essential for viral replication and transcription. Beyond packaging viral RNA, NCs also play important roles in virus replication, transcription, assembly, and budding by interacting with viral and host cellular proteins. Additionally, NCs can inhibit interferon signaling response and function in cell stress response, such as inducing apoptosis. Finally, NCs can be the target of vaccines, benefiting from their conserved gene sequences. Here, we summarize important findings regarding the additional functions of NCs as much more than structural RNA‐binding proteins, with specific emphasis on (1) their association with the viral life cycle, (2) their association with host cells, and (3) as ideal candidates for vaccine development. WIREs RNA 2016, 7:213–226. doi: 10.1002/wrna.1326 1.. RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes; 2.. RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications; 3.. Translation > Translation Regulation.
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