Project titleIdentification of Factors That Regulate U6atac Instability in Breast Cancer Cells

Eukaryotic DNA consists of protein- coding sequences, referred to as exons, that are disrupted by non-protein coding sequences, referred to as introns. Younis et al. (2013) discovered that the catalytic U6atac snRNA from the minor spliceosome was highly unstable in HeLa cells, even though genes containing minor introns were highly dependent on them. Furthermore, they discovered that the abundance of U6atac can be increased by activating p38MAPK, which increases the splicing efficiency of U6atac and thus increase the expression of these mRNAs. Thus, minor introns are molecular switches of gene regulation expression that rely on U6atac levels. The Younis lab has also shown that the minor intron of the tumor suppressor PTEN is inefficiently spliced in breast cancer cells, which contributes to their aggressive phenotype. However, it is still unclear whether the stability of U6atac is regulated in breast cancer leading to inefficient splicing of minor introns in specific genes, such as tumor suppressor genes. This project aims to measure the stability of U6atac and its consequences on the splicing efficiency of minor intron containing genes in MCF-7 breast cancer cells. Given the functional importance of minor intron containing genes in cancer, such as PTEN, and the fact that the splicing of minor introns is rate-limiting for the genes that contain them, understanding how minor introns are regulated in breast cancer will shed new light on this critical step in gene expression and could open the door for novel therapeutic approaches. 

Primary contact nameAmeera Al-Janahi
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Students/participant(s) programs
  • Biological Sciences
Faculty advisor(s)
Advisor name Email Affiliation
Ihab Younis Carnegie Mellon University
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  • Biological Sciences