Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

BIOGENESIS AND FUNCTIONAL APPLICATIONS OF PIWI INTERACTING RNAs (piRNAs)

Balaratnam, Sumirtha
http://rave.ohiolink.edu/etdc/view?acc_num=kent1531753741509242

Abstract Details

2018, PHD, Kent State University, College of Arts and Sciences / Department of Chemistry.
The piwi interacting RNAs (piRNAs) are small non-coding RNAs with mostly 24-32 nucleotides in length. The piRNAs are defined by their ability to specifically bind to the PIWI proteins, a requirement for their functions. The piRNAs are involved in germline development, transposon control, transcriptional and post-transcriptional gene regulation. However, piRNA mediated post-transcriptional gene regulation in human somatic cells is not well understood. We discovered a human piRNA (piR-FTH1) that negatively regulates the FTH1 expression at the post-transcriptional level in MDA-MB 231 triple negative breast cancer cells. Furthermore, we established that piR-FTH1 knocks down the FTH1 mRNA through the piR-FTH1-HIWI-RISC pathway by using the HIWI2 and HILI proteins. We determined that FTH1 repression by piR-FTH1 increases the sensitivity of the chemotherapeutic agent Doxorubicin by a remarkable 20-fold. In a related project, we investigated the role of piRNA structure in its function. Interestingly, the piRNAs do not have any defined secondary structure. Using bioinformatics analysis, we discovered the presence of putative G-quadruplex (GQ)-forming sequences in human piRNAs that are higher in number compared to the piRNA pools of other organisms that were analyzed. Using one GQ forming human piRNA sequence (piR-48164), we showed that formation of GQ structure in the piRNA led to inhibitions of the PIWI protein binding and target gene silencing in vitro and in cellulo. These studies unraveled the role of a non- canonical secondary structure GQ in the piRNA function and added a new layer of regulation in piRNA function. It has been reported previously that after the PIWI protein degradations, piRNAs become unprotected and undergo elimination. Prior to this study, the degradation mechanism of piRNA is unknown. We found that presence of 3' methylation of piRNA prevents its degradation through the exosome mediated decay pathway. We established that XRN1 and XRN2 are two 5' to 3' exoribonucleases involved in the degradation of piRNA in the cell. This study provides the basic information about the regulation in piRNA biogenesis and turnover. Since the piRNA studies are part of an emerging field, our findings will lay the ground rules for various aspects of piRNA function, metabolism and its use as a therapeutic agent in somatic cells
Soumitra Basu (Advisor)
Soumitra Basu (Committee Chair)
Gail Fraizer (Committee Member)
Paul Sampson (Committee Member)
Sanjaya Abeysirigunawardena (Committee Member)
Jennifer McDonough (Committee Member)
199 p.
Biochemistry; Biomedical Research; Cellular Biology; Chemistry; Inorganic Chemistry; Molecular Biology
piRNA, post-transcriptional gene regulation, RNA degradation, G-quadruplex, divalent metal cations, RNA, ferritin heavy chain protein, HIWI, HILI, HIWI2, XRN1, XRN2, exosome and RNA methylation,

Recommended Citations

Citations

  • Balaratnam, S. (2018). BIOGENESIS AND FUNCTIONAL APPLICATIONS OF PIWI INTERACTING RNAs (piRNAs) [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1531753741509242

    APA Style (7th edition)

  • Balaratnam, Sumirtha. BIOGENESIS AND FUNCTIONAL APPLICATIONS OF PIWI INTERACTING RNAs (piRNAs) . 2018. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1531753741509242.

    MLA Style (8th edition)

  • Balaratnam, Sumirtha. "BIOGENESIS AND FUNCTIONAL APPLICATIONS OF PIWI INTERACTING RNAs (piRNAs) ." Doctoral dissertation, Kent State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1531753741509242

    Chicago Manual of Style (17th edition)

kent1531753741509242
201
© 2018, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.