Probing Nuclear HSATII Biomolecular Condensates
Document Type
Poster Session
Publication Date
2-8-2024
Published In
Biophysical Journal
Abstract
Human satellite sequence II (HSATII) is a tandemly repeated pericentric and heterochromatic sequence that is transcriptionally silent in normal human cells, yet in cancer cells HSATII RNA is aberrantly expressed and accumulates large nuclear foci that remain in cis at their sites of transcription. Expression and aggregation of HSATII RNA is concomitant with sequestration of key chromatin regulatory proteins known to phase separate including MeCP2. While HSATII expression is highly correlated with higher grade tumors in various epithelial cancer cell lines, the effect of its nuclear misregulation is poorly understood. Due to the upregulation of HSATII RNA expression in cancer, accumulation of the HSATII RNA in cis, sequestration of key regulatory phase-separating proteins, and its repetitive nature, we hypothesized that HSATII RNA is a molecular scaffold that nucleates and forms phase-separated biomolecular condensates in vivo. Condensates are increasingly recognized as important for cellular function and dysfunction. Here, we present evidence that HSATII RNA assembles into biomolecular condensates via in vitro assays. We also employ an in vivo disruption assay that utilizes doxorubicin and 1,6-hexanediol, both drugs known to specifically target and disrupt condensates in vivo. Treatment with both these drugs resulted in significant redistribution of HSATII RNA in living cells. Characterizing HSATII RNA focal accumulations as condensates provides a mechanistic account for pathological phenotypes in cancer. While this study serves to demonstrate that HSATII RNA foci can form condensates, it also has broader implications for drug development in cancer therapeutics.
Conference
Biophysical Society Annual Meeting 2024
Conference Dates
February 10-14, 2024
Conference Location
Philadelphia, PA
Recommended Citation
Thembalami Dube , '24; Christina Rabeler; and Dawn M. Carone.
(2024).
"Probing Nuclear HSATII Biomolecular Condensates".
Biophysical Journal.
Volume 123,
Issue 3, suppl. 1.
219a-219a.
DOI: 10.1016/j.bpj.2023.11.1388
https://works.swarthmore.edu/fac-biology/697
