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Why did that cancer cell become drug-resistant?
Summary
Harvard researchers developed TimeVault, a technique that stores messenger RNA inside natural vault particles to preserve past gene-expression snapshots, and they used it to record cellular responses to stress and to examine how some cancer cells developed drug resistance.
Content
Harvard researchers report a technique called TimeVault that creates tiny archives of messenger RNA inside naturally occurring vault particles. The engineered system links poly(A) binding proteins to vault-forming proteins so transcripts are enclosed and shielded from normal degradation. In experiments the vaults extended RNA preservation from about 17 hours to roughly 132 hours, and vault contents are passed to daughter cells during division. The team tested the method on heat shock and low-oxygen conditions and applied it to study why some cancer cells became resistant to drugs.
Key findings:
- TimeVault uses poly(A) binding proteins attached to vault-forming proteins to capture and enclose mRNA inside cellular vault particles.
- Vault-enclosed RNA showed an increased half-life from about 17 hours in the cytoplasm to about 132 hours inside vaults in laboratory tests.
- Vault contents can be chemically released later to reconstruct a transcriptome snapshot of past gene activity.
- The vault archives are inherited by daughter cells when a cell divides.
- Researchers demonstrated preserved signatures after heat shock and hypoxia and used the approach to examine cellular changes associated with drug resistance in cancer cells.
Summary:
The method provides a way to link a cell's past gene-expression state to its later behavior and offers a new tool for studying processes such as differentiation, stress responses, adaptation, and drug resistance. Thus far TimeVault has recorded individual timepoints and is published in Science; researchers hope to adapt it to capture multiple timepoints, while further applications are under study.
