Non-coding RNAs, stem cells, germline, Drosophila, cancer, cellular bodies, regulation of gene expression.
Noncoding RNAs (ncRNAs) have emerged as potent agents for gene regulation during normal development and in diseases such as cancer. Introns are widely considered as junk sequences interspersed between coding exons in genes of eukaryotes and viruses. Recent studies have identified various forms of stable intronic sequence RNAs (linear and circular) that belong to a novel class of long ncRNAs that regulate gene expression (Pek and Okamura 2015; Osman et al., 2016; Pek 2018). Our group has discovered many sisRNAs in Drosophila, and showed that sisRNAs engage in regulatory feedback loops and play important roles in stem cell homeostasis and development (Pek 2018). sisR-1 functions in a negative feedback loop in repressing its parental gene for proper germline stem cell maintenance in the ovary (Figure 1) (Pek et al., 2015; Wong et al., 2017). On the other hand, sisR-4 is a maternally-deposited circular sisRNA that promotes the expression of its parental gene that is essential for embryonic development (Figure 2) (Tay and Pek 2017).
We are interested in studying more sisRNAs to uncover more regulatory pathways important for basic biological processes. During the course of our study, we discovered a previously unidentified nuclear body called “satellite body” (Figure 3) (Wong et al., 2017). Interestingly, satellite bodies localize to regions of high sisRNA production, suggesting that they are involved in sisRNA metabolism in the nucleus.
Currently, we are investigating the composition and molecular function of satellite body. Recent studies have shown that the roles of sisRNAs in regulatory feedback loops are conserved in cancer tissues. We are currently extending our research on sisRNA/ncRNA to cancer with an emphasis on prostate cancer. We will focus on 3 main aspects: 1. Molecular mechanisms, 2. Novel biomarkers, and 3. Disease modelling in Drosophila.
Osman, I. and Pek, J.W. (2018). A sisRNA/miRNA axis prevents loss of germline stem cells during starvation in Drosophila. Stem Cell Reports 11, 4-12.
Ng, A.Y.E, Peralta, K.R.G. and Pek, J.W. (2018). Germline stem cell heterogeneity supports homeostasis in Drosophila. Stem Cell Reports 11, 13-21.
Ng, S.S.J., Zheng, R.T., Osman, I. and Pek, J.W. (2018). Generation of Drosophila sisRNAs by independent transcription from cognate introns. iScience 4, 68-75.
Wong, J.T., Akhbar, F., Ng, A.Y.E, Tay, M.L.I., Loi, G.J.E. and Pek, J.W.* (2017). DIP1 modulates stem cell homeostasis in Drosophila through regulation of sisR-1. Nat. Comm. 8, 759. (*corresponding author)
Tay, M.,L.I. and Pek, J.W.* (2017). Maternally inherited stable intronic sequence RNA triggers a self-reinforcing feedback loop during development. Curr. Biol. 27, 1062-1067. (*corresponding author)
Pek, J.W.*, Osman, I., Tay, M.,L.I. and Zheng, R.T. (2015). Stable intronic sequence RNAs have possible regulatory roles in Drosophila melanogaster. J. Cell Biol. 211, 243-251. (*corresponding author)
Pek, J.W., Ng, B.F. and Kai, T. (2012). Polo-mediated phosphorylation of Maelstrom regulates oocyte determination during oogenesis in Drosophila. Development 139, 4505-4513.
Pek, J.W. and Kai, T. (2011). DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway promote mitotic chromosome segregation. Proc. Natl. Acad. Sci. U.S.A. 108, 12007-12012.
Pek, J.W. and Kai, T. (2011). A role for Vasa in regulating mitotic chromosome condensation in Drosophila. Curr. Biol. 21, 39-44.
Pek, J.W., Lim, A.K. and Kai, T. (2009). Drosophila Maelstrom ensures proper germline stem cell lineage differentiation by repressing microRNA-7. Dev. Cell 17, 417-424. Review articles
Chan, S.N. and Pek, J.W. (2019). Stable intronic sequence RNAs (sisRNAs): an expanding universe. Trends Biochem. Sci. 44, 258-272. Pek, J.W. (2018). Stable intronic sequence RNAs engage in feedback loops. Trends Genet. 34, 330-332.
Osman, I., Tay, M.,L.I. and Pek, J.W.* (2016). Stable intronic sequence RNAs (sisRNAs): a new layer of gene regulation. Cell. Mol. Life Sci. 73, 3507-3519. (*corresponding author)
Pek, J.W.* and Okamura, K.* (2015). Regulatory RNAs discovered in unexpected places. WIREs RNA 6, 671-686. (*co-corresponding authors)
Pek, J.W.*, Anand, A. and Kai, T.* (2012). Tudor domain proteins in development. Development 139, 2255-2266. (*co-corresponding authors)
Pek, J.W.*, Patil, V.S.* and Kai, T. (2012). piRNA pathway and the potential processing site, the nuage, in the Drosophila germline. Dev. Growth Differ. 54, 66-77. (*co-first authors)
Pek, J.W.* and Kai, T.* (2011). Non-coding RNAs enter mitosis: functions, conservation and implications. Cell Div. 6, 6. (*co-corresponding authors)
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