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Functional Characterization of Human LncRNA JPX

  • Author(s): Karner, Heather
  • Advisor(s): Sun, Sha
  • et al.
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Abstract

ABSTRACT OF THE DISSERTATION

Functional Characterization of Human LncRNA JPX

By

Heather Karner

Doctor of Philosophy in Biological Sciences

University of California, Irvine, 2019

Assistant Professor Sha Sun, Chair

Long noncoding RNAs are present in all eukaryotes, but knowledge of their function and mechanisms are lacking. In this dissertation, I have worked toward characterizing a human lncRNA known as JPX. In mice, this lncRNA has been proposed to be the activator of the master regulator of X chromosome inactivation, lncRNA Xist. My research provides evidence that human lncRNA JPX is capable of this function as well, through comparative sequence, structural, and functional analyses. Human JPX, despite sequence and structural divergence from its mouse homolog, robustly binds CTCF—a protein that is known to sit on the Xist promoter and inhibit expression. Most interestingly, the human JPX complemented the deleterious effect of a heterozygous loss of Jpx in mouse embryonic stem cells and returned these cells to wild type viability and morphology, as well as increased Xist expression. The differences between the two lncRNAs begs the question of whether lncRNA JPX has gained new functions in humans. To study this, I investigated JPX and XIST in ovarian cancer. This cancer tends to be discovered at later, more aggressive stages. It was found that these later stages also tend to have decreased expression of JPX and XIST in patients. So far, my research indicates that these lncRNAs may be engaged in biological pathways involved in tumor suppression, and their loss could lead to the progression and metastasis of ovarian cancer.

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This item is under embargo until April 13, 2022.