近年研究主題

小片段非編碼核糖核酸基因轉錄及轉譯調控之分子機制

研究室簡介

小片段非編碼核糖核酸 (small non-coding RNAs) 是細胞內自生的短核甘酸鏈。最新的研究顯示這種小片段RNAs具有調控基因表現的能力。其機轉乃是作用在基因轉錄後的各階段,進而降低蛋白質表現量。RNA干擾 (RNA interference, RNAi)的現象即是小片段 RNA調控目標基因的一種應用。人體細胞中內生性的微RNA (microRNAs)也是small non-coding RNA之一種。microRNA (miRNAs) 利用其序列的專一性來辨識目標基因,並藉由與其結合的蛋白複合體之作用,來抑制目標基因轉譯的效率或增加該基因mRNA降解的速率,最終抑制基因產物的表現。由於miRNAs具有調控基因表現的作用,近年來的實驗證明miRNAs具有許多細胞生理上的功能,並且在胚胎發育、宿主對抗病原體以及癌細胞病理病程發展上都扮演重要角色。然而目前多數的研究僅止於描述某一特定miRNA的表現與疾病或發育過程的相關性連結以及現象,對於詳細的作用機制仍然不甚了解。

研究室研究方向將著重於miRNA造成轉錄抑制效果的分子機轉,預定的研究計畫包括:
  1. miRNA結合蛋白複合體的組成分析: 利用功能基因體學的研究方法,尋找miRNA造成轉錄抑制效果的功能性蛋白。
  2. miRNA轉錄抑制複合體在細胞內的分布組成,以及在不同環境刺激因子調節下,該蛋白複合體在胞內微結構分布的轉換與miRNA作用活性的關連性。
  3. 轉錄抑制蛋白的表現與miRNA協同作用在胚胎早期發育以及腫瘤細胞癌化的影響。

代表著作

Publications

期刊論文 Journal
  1. Huang JH, Ku WC , Chen YC, Chang YL, and Chu CY*. “Dual mechanisms regulate the nucleocytoplasmic localization of human DDX6.” Sci Rep. 2017 Feb 20;7:42853. doi: 10.1038/srep42853.
  2. Sheen YH, Liao YH, Lin MS, Chu CY, Ho BY, Hsieh MC, Chen PC, Cha ST, Jeng YM, Chang CC, Chiu HC, Jee SH, Kuo ML, and Chu CY. “IMP-3 Promotes Migration and Invasion of Melanoma Cells by Modulating the Expression of HMGA2 and Predicts Poor Prognosis in Melanoma.” J Invest Dermatol. 2015 Apr;135(4):1065-73. .
  3. Baco M, Chu CY, Bouet S, Rogel-Gaillard C, Bourneuf E, Le Provost F, Chu CY and Vincent-Naulleau S. “Analysis of melanoma-related microRNAs expression during the spontaneous regression of cutaneous melanomas in MeLiM pigs.” Pigment Cell Melanoma Res, 2014 Jul;27(4):668-70. .
  4. Lu YC, Chen CN, Chu CY, Lu J, Wang BJ, Chen CH, Huang MC, Lin TH, Pan CC, Chen SS, Hsu WM, Liao YF, Wu PY, Hsia HY, Chang CC, Lee H. “Calreticulin activates β1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells.” Biochem J, 15;460(1):69-78. doi: 10.1042/BJ20131424. .
  5. Chang YT, Lin CY, Tsai CY, Siva VS, Chu CY, Tsai HJ, and Song YL. “The New Face of the Old Molecules: Crustin Pm4 and Transglutaminase Type I Serving as RNPs Down-Regulate Astakine-Mediated Hematopoiesis.” PLoS ONE 2013 8(8): e72793.
  6. Lu CC, Li Z, Chu CY, Feng J, Feng J, Sun R, and Rana TM*. “MicroRNAs encoded by Kaposi's sarcoma-associated herpesvirus regulate viral life cycle.” EMBO Rep. 2010 Oct;11(10):784-90.
  7. James V, Zhang Y, Foxler DE, de Moor CH, Kong YW, Webb TM, Self TJ, Feng Y, Lagos D, Chu CY, Rana TM, Morley SJ, Longmore GD, Bushell M, and Sharp TV. “LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing.” Proc Natl Acad Sci USA. 2010 Jul 13;107(28): 12499-504.
  8. Nathans R, Chu CY, Serquina A, Lu C, Cao H, and Rana TM. “Defense against HIV-1 is mediated by P bodies and a cellular microRNA”. Mol Cell 2009 Jun: 34(6): 696-709.
  9. Chu CY, and Rana TM, “Potent RNAi by short RNA trigger”. RNA 2008 14: 1714-19.
  10. Chu CY, and Rana TM. “Small RNAs: regulators and guardians of the genome.” J Cell Physiol. 2007 Nov;213(2):412-9. Review.
  11. Chu CY, and Rana TM. “Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54.” PLoS Biol. 2006 Jul;4(7):e210.
  12. Chiu YL, Dinesh CU, Chu CY, Ali A, Brown KM, Cao H, Rana TM. “Dissecting RNA-interference pathway with small molecules.” Chem Biol. 2005 Jun;12(6):643-8.
  13. Brown KM, Chu CY, Rana TM. “Target accessibility dictates the potency of human RISC.” Nat Struct Mol Biol. 2005 May;12(5):469-70.
  14. Ping YH, Chu CY, Cao H, Jacque JM, Stevenson M, Rana TM. “Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5.” Retrovirology. 2004 Dec 27;1:46.
  15. Chiu YL, Ali A, Chu CY, Cao H, Rana TM. “Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells.” Chem Biol. 2004 Aug;11(8):1165-75.

研討會論文
Conference
PRESENTATION:
  1. Chu CY, and Rana TM. “Chemical modification of small interfering RNAs imparts functional insight into the molecular mechanism of RNA interference.” 9th annual meeting of the RNA society. June 2004, Madison, WI.
  2. Chu CY, and Rana TM. “Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54.” 7th annual poster symposium of Burnham Science Network. November 2008, La Jolla, CA.

專書章節
Literature
Book Chapters:
  1. Chia-Ying Chu and Tariq M. Rana. (2009) “Structure and Gene-Silencing Mechanisms of Small Noncoding RNAs,” in Non-Protein Coding RNAs. Springer Series in Biophysics 13. (Walter NG et al. eds.) Springer-Verlag Berlin Heidelberg.

開設課程

  • B43 U1250 基因體學
  • B41 D0100 博士班專題討論
  • B01 101B1普通生物學
  • B01 106B1普通生物學實驗
  • B01 40010 書報討論
  • 核醣核酸生物學 RNA Biology