Poster number 155 submitted by Christina Rabeler
Ectopic expression of HSATII RNA results in nuclear focal accumulations and chromatin defects
Christina A. Rabeler (Department of Biology, Swarthmore College), Emily K. Ferrari (University of Pennsylvania), Lia R. DAlessandro (Broad Institute), Dawn M. Carone (Department of Biology, Swarthmore College)
Human Satellite II (HSATII) is a tandemly repeated pericentric satellite sequence that is transcriptionally silenced in normal cells yet is aberrantly expressed in many types of cancer cells, where the RNA forms large nuclear foci in cis. These focal accumulations of HSATII RNA have been shown to recruit and sequester regulatory proteins including methyl-CpG binding protein 2 (MeCP2). In order to examine the role of HSATII RNA, cells which do not normally transcribe HSATII were transfected to stably express this RNA. Both HeLa and primary fibroblast cells which ectopically expressed HSATII RNA were seen to aggregate the RNA in nuclear foci in cis and also accumulate MeCP2 onto those foci. Additionally, an increase in cellular division defects including lagging chromosomes and chromatin bridges was observed in cells after long-term ectopic expression of HSATII. These results suggest that forced expression of HSATII RNA leads to nuclear accumulation and recruitment of protein binding partners that ultimately results in cell division defects, thus suggesting a role for HSATII expression in cancer.
Keywords: HSATII, lncRNA, chromatin instability