https://scholar.korea.ac.kr/handle/2021.sw.korea/2474 Sun, 05 Apr 2026 17:06:57 GMT 2026-04-05T17:06:57Z https://scholar.korea.ac.kr/handle/2021.sw.korea/54217 Title: Roles for Drosophila cap1 2 '-O-ribose methyltransferase in the small RNA silencing pathway associated with Argonaute 2 Authors: Lee, Seungjae; Hong, Jae-Sang; Lim, Do-Hwan; Lee, Young Sik Abstract: Cap1 2 '-O-ribose methyltransferase (CMTR1) modifies RNA transcripts containing the 7-methylguanosine cap via 2 '-O-ribose methylation of the first transcribed nucleotide, yielding cap1 structures. However, the role of CMTR1 in small RNA-mediated gene silencing remains unknown. Here, we identified and characterized a Drosophila CMTR1 gene (dCMTR1) mutation. We found that the catalytic activity of dCMTR1 was involved in the biogenesis of small interfering RNAs (siRNAs) but not microRNAs. Additionally, dCMTR1 interacted with R2D2, a key component for the assembly of the RNA-induced silencing complex (RISC) containing Argonaute 2 (Ago2). Consistent with this finding, loss of dCMTR1 function impaired RISC assembly by inhibiting the unwinding of Ago2-bound siRNA duplexes, thus preventing the retention of the guide strand. Moreover, dCMTR1 is unlikely to modify siRNAs during RISC assembly. Collectively, our data indicate that dCMTR1 is a positive regulator of the small RNA pathway associated with Ago2 with roles in both siRNA biogenesis and RISC assembly. Sat, 01 Aug 2020 00:00:00 GMT https://scholar.korea.ac.kr/handle/2021.sw.korea/54217 2020-08-01T00:00:00Z https://scholar.korea.ac.kr/handle/2021.sw.korea/56203 Title: The conserved microRNA miR-8-3p coordinates the expression of V-ATPase subunits to regulate ecdysone biosynthesis for Drosophila metamorphosis Authors: Lim, Do-Hwan; Lee, Seungjae; Choi, Min-Seok; Han, Jee Yun; Seong, Youngmo; Na, Dokyun; Kwon, Young-Soo; Lee, Young Sik Abstract: The steroid hormone ecdysone is the central regulator of insect metamorphosis, during which a growing, immature larva is remodeled, through pupal stages, to a reproductive adult. However, the underlying mechanisms of ecdysone-mediated metamorphosis remain to be fully elucidated. Here, we identified metamorphosis-associated microRNAs (miRNAs) and their potential targets by cross-linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 protein in Drosophila. Interestingly, miR-8-3p targeted five Vha genes encoding distinct subunits of vacuolar H+-ATPase (V-ATPase), which has a vital role in the organellar acidification. The expression of ecdysone-responsive miR-8-3p is normally downregulated during Drosophila metamorphosis, but temporary overexpression of miR-8-3p in the whole body at the end of larval development led to defects in metamorphosis and survival, hallmarks of aberrant ecdysone signaling. In addition, miR-8-3p was expressed in the prothoracic gland (PG), which produces and releases ecdysone in response to prothoracicotropic hormone (PTTH). Notably, overexpression of miR-8-3p or knockdown of its Vha targets in the PG resulted in larger than normal, ecdysone-deficient larvae that failed to develop into the pupal stage but could be rescued by ecdysone feeding. Moreover, these animals showed defective PTTH signaling with a concomitant decrease in the expression of ecdysone biosynthetic genes. We also demonstrated that the regulatory network between the conserved miR-8-3p/miR-200 family and V-ATPase was functional in human cells. Consequently, our data indicate that the coordinated regulation of V-ATPase subunits by miR-8-3p is involved in Drosophila metamorphosis by controlling the ecdysone biosynthesis. Fri, 01 May 2020 00:00:00 GMT https://scholar.korea.ac.kr/handle/2021.sw.korea/56203 2020-05-01T00:00:00Z https://scholar.korea.ac.kr/handle/2021.sw.korea/63570 Title: Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression Authors: Bae, Joonbeom; Choi, Sang-Pil; Isono, Kyoichi; Lee, Ji Yoon; Park, Si-Won; Choi, Chang-Yong; Han, Jihye; Kim, Sang-Noon; Lee, Han-Hyoung; Park, Kyungmin; Jin, Hyun Yong; Lee, Suk Jun; Park, Chung-Gyu; Koseki, Haruhiko; Lee, Young Sik; Chun, Taehoon Abstract: The timely mobilization of hematopoietic stem and progenitor cells (HSPCs) is essential for maintaining hematopoietic and tissue leukocyte homeostasis. Understanding how HSPCs migrate between bone marrow (BM) and peripheral tissues is of great significance in the clinical setting, where therapeutic strategies for modulating their migration capacity determine the clinical outcome. Here, we identify an epigenetic regulator, Phc2, as a critical modulator of HSPC trafficking. The genetic ablation of Phc2 in mice causes a severe defect in HSPC mobilization through the derepression of Vcam1 in bone marrow stromal cells (BMSCs), ultimately leading to a systemic immunodeficiency. Moreover, the pharmacological inhibition of VCAM-1 in Phc2-deficient mice reverses the symptoms. We further determine that Phc2-dependent Vcam1 repression in BMSCs is mediated by the epigenetic regulation of H3K27me3 and H2AK119ub. Together, our data demonstrate a cell-extrinsic role for Phc2 in controlling the mobilization of HSPCs by finely tuning their bone marrow niche. Fri, 02 Aug 2019 00:00:00 GMT https://scholar.korea.ac.kr/handle/2021.sw.korea/63570 2019-08-02T00:00:00Z https://scholar.korea.ac.kr/handle/2021.sw.korea/64861 Title: MicroRNA miR-252 targets mbt to control the developmental growth of Drosophila Authors: Lim, D. -H.; Lee, S.; Han, J. Y.; Choi, M. -S.; Hong, J. -S.; Lee, Y. S. Abstract: Developmental growth is an intricate process involving the coordinated regulation of the expression of various genes, and microRNAs (miRNAs) play crucial roles in diverse processes throughout animal development. The ecdysone-responsive miRNA, miR-252, is normally upregulated during the pupal and adult stages of Drosophila development. Here, we found that overexpression of miR-252 in the larval fat body decreased total tissue mass through a reduction in both cell size and cell number, causing a concomitant decrease in larval size. Furthermore, miR-252 overexpression led to a delayed larval-to-pupal transition with defective anterior spiracle eversion, as well as a decrease in adult size and mass. Conversely, adult flies lacking miR-252 showed an increase in mass compared with control flies. We found that miR-252 directly targeted mbt, encoding a p21-activated kinase, to repress its expression. Notably, co-overexpression of mbt rescued the developmental and growth defects associated with miR-252 overexpression, indicating that mbt is a biologically relevant target of miR-252. Overall, our data support a role for the ecdysone/miR-252/mbt regulatory axis in growth control during Drosophila development. Sat, 01 Jun 2019 00:00:00 GMT https://scholar.korea.ac.kr/handle/2021.sw.korea/64861 2019-06-01T00:00:00Z