Dr. Tarn, Woan-Yuh 譚婉玉 博士

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Dr. Tarn, Woan-Yuh
譚婉玉 博士

Distinguished Research Fellow
特聘研究員



  • Ph.D. National Tsing Hua University
    Postdoc Assoc. Yale University

  • 02-27899015 (Lab) (Room No: N223)
  • 02-26523052
  • 02-27829142 (Fax)
Specialty:

 

  1. mRNA splicing in neuron
  2. translational control in cancer
  3. long non-coding RNA

RESEARCH

Post-transcriptional regulation in neuronal and cancer cells

Post-transcriptional control is important for eukaryotic gene expression and cell biology and physiology. We aim to have a comprehensive understanding of how regulation of mRNA biogenesis impacts cell function, in which we focused on alternative splicing and translational control. Alternative splicing provides a means for development- and tissue-specific gene expression. We investigate how alternative splicing programs neuronal cell differentiation and impacts brain development. Our previous studies reveal that RBM4-mediated alternative splicing is important for neuronal cell differentiation and radial glial migration during brain development. Rbm4 knockout mice exhibited abnormalities of cerebellar foliation. Therefore, we currently examine how RBM4-mediated splicing regulation influences cerebellar development. In our second project, we study how RNA helicase DDX3-mediated translational control influences cancer progression. We recently report that DDX3 promotes the translation of several stress-induced oncogenes by counteracting the suppressive effects of upstream open reading frames. Moreover, DDX3 promotes the translation of secretory oncogenic factors via its association with the signal recognition particle on the ER. Cancer-derived mutants of DDX3 exert higher potential to translate those pro-tumorigenic factors and hence contribute to the pro-tumorigenic microenvironment (submitted). Moreover, we previously investigated non-canonical functions of the post-splicing exon-junction complex. We recently found that one of its components (Y14) is involved in DNA damage repair and genomic stability maintenance. Y14 deficiency causes thrombocytopenia. We have generated a mouse model and uncovered that the Y14-p53 regulation circuit contributes to megakaryocyte differentiation and platelet production (submitted). We would continue to unveil the importance of RNA regulation. 

研究介紹

神經及癌細胞之後轉錄基因調控

 

轉錄後調控對於基因表達和細胞生理功能有極重要的影響,因此我們希望全面了解 mRNA的調控 (特別是選擇性剪接和轉譯控制) 如何影響基因的表現及細胞的功能。選擇性剪接會產生具有發育和組織特異性功能的基因產物,我們研究選擇性剪接如何影響神經元細胞分化及大腦發育。我們先前的研究曾顯示經由RBM4調控的選擇性剪接對於大腦發育過程中的神經元細胞分化和神經幹細胞遷移很重要。 由於Rbm4 基因剔除小鼠表有小腦葉發育異常的現象,因此我們目前的研究希望了解 RBM4 調控的選擇性剪接如何影響小腦發育。在我們的第二個計劃中,我們研究 RNA 解旋酶 DDX3 所調控的轉譯控制如何影響癌症進展。我們最近曾報導DDX3 藉由抵消上游ORF的抑制作用來促進被壓力誘導的致癌基因之轉譯。此外,DDX3 會藉由與內質網信號識別複合體的結合促進分泌性致癌因子的轉譯。由癌症衍生的DDX3突變具有更高的轉譯促進能力,因此形成有助腫瘤發生的微環境,抑制 DDX3 將成為未來癌症的治療策略。此外,我們之前曾研究剪接後外顯子連接複合體的非典型功能,我們最近發現Y14及非編碼 RNA會參與 DNA 損傷修復和基因組穩定性維護。由於 Y14缺失會導致血小板減少。我們為此建立了一個小鼠模型,並發現 Y14-p53 調節迴路有助於巨核細胞分化和血小板生成。我們將繼續研究RNA生物學的重要議題,特別針對mRNA剪接與轉譯調控對生理和發育的影響以及在醫學上的應用,將有更進一步認識。

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