Despite the cell being the most basic unit of life, to say that it is “basic” is an understatement of what cells are composed of. The cell is so highly complex and diverse that research dedicated to its study has continuously brought to light novel discoveries on its function in the last hundred years. To Leonard Rome and Nancy Kedersha, this undeniable fact has once again proven itself while trying to isolate cell vesicles in 1986. They discovered football-shaped particles, which they later on termed “vaults,” after Kedersha mentioned how they look like vaulted cathedral ceilings.
In spite of being one of the largest known naturally occurring particles in the cell, standing at roughly 70 nm, these little particles are quite simple. Vaults are made up of three proteins and small untranslated RNA molecules. They have a highly conserved evolutionary unit called the “Major Vault Protein” (MVP), which aggregates together to form the casing of these vaults. Vaults are abundantly present in the cytoplasm of eukaryotic cells, and they were found to be associated with cytoskeletal elements and, occasionally, with the nuclear envelope.
Amidst all that has been elucidated, much research is yet to be done to truly understand what these particles do. According to studies, these vaults have been extremely conserved over time, and Rome would contend that they existed even in the last eukaryotic common ancestor. The earliest jawed fish were found to contain vault RNA (vtRNA)!
These questions have continuously challenged knowledge on vaults, and from these arose opportunities to explore how they can be used in real-world applications. Because they are highly conserved and feature both a unique structure and empty space, vaults have gained significant attention in recent research, where they are proposed to act as cargo transporters for adeno-associated viruses (AAVs) used in gene therapy. Another potential application, although discontinued, involves their use to transport CCL21, a specialized protein that can help the body’s immune response against cancer.
Vaults, one of the earlier discoveries in the molecular landscape, remain enigmatic and full of untapped potential. The story of the vault reminds us that science isn’t a collection of final answers but a process—a journey of trial, error, insight, and revision. It’s a collective endeavor that thrives on openness, creativity, and collaboration.
Berger, W., Steiner, E., Grusch, M., Elbling, L., & Micksche, M. (2008). Vaults and the major vault protein: Novel roles in signal pathway regulation and immunity. Cellular and Molecular Life Sciences, 66(1), 43–61. https://doi.org/10.1007/s00018-008-8364-z
Collins, L. T., Beatty, W., Moyo, B., Alves-Bezerra, M., Hurley, A., Lou, Q., Zhou, Z. H., Lagor, W., Bao, G., Selvarangan Ponnazhagan, McNally, R., Rome, L. H., & Curiel, D. T. (2023). Encapsulation of AAVs into protein vault nanoparticles as a novel solution to gene therapy’s neutralizing antibody problem. BioRxiv (Cold Spring Harbor Laboratory). https://doi.org/10.1101/2023.11.29.569229
Kar, U. K., Srivastava, M. K., Andersson, Å., Baratelli, F., Huang, M., Kickhoefer, V. A., Dubinett, S. M., Rome, L. H., & Sharma, S. (2011). Novel CCL21-Vault Nanocapsule Intratumoral Delivery Inhibits Lung Cancer Growth. PLoS ONE, 6(5), e18758. https://doi.org/10.1371/journal.pone.0018758
Kedersha, N. L., & Rome, L. H. (1986). Isolation and characterization of a novel ribonucleoprotein particle: large structures contain a single species of small RNA. The Journal of Cell Biology, 103(3), 699–709. https://doi.org/10.1083/jcb.103.3.699
Stadler, P. F., Chen, J. J.-L. ., Hackermuller, J., Hoffmann, S., Horn, F., Khaitovich, P., Kretzschmar, A. K., Mosig, A., Prohaska, S. J., Qi, X., Schutt, K., & Ullmann, K. (2009). Evolution of Vault RNAs. Molecular Biology and Evolution, 26(9), 1975–1991. https://doi.org/10.1093/molbev/msp112
Travis, J. (2024). The Vault Guy: Leonard Rome’s lab discovered an odd, abundant component of cells in the 1980s—and he’s still trying to figure out what it does. Science.org. https://www.science.org/content/article/biologist-aims-solve-cell-s-biggest-mystery-could-it-help-cancer-patients-too
The key to “the vault.” (2024). Royal Society of Biology. https://www.rsb.org.uk/biologist-features/unlocking-the-vault
van Zon, A., Mossink, M. H., Schoester, M., Scheffer, G. L., Scheper, R. J., Sonneveld, P., & Wiemer, E. A. C. (2001). Multiple Human Vault RNAs. Journal of Biological Chemistry, 276(40), 37715–37721. https://doi.org/10.1074/jbc.m106055200
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