Dr. Tarn, Woan-Yuh 譚婉玉 博士

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Dr. Tarn, Woan-Yuh
譚婉玉 博士

Research Fellow
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 metabolism
  2. post-transcriptional control

RESEARCH

Post-transcriptional regulation in neuronal and cancer cells

 

Post-transcriptional control is important for eukaryotic gene expression and cellular function. We aim to have a comprehensive understanding of the mechanisms of mRNA metabolism and its impact on cell function, for which we focused on alternative splicing and translational control. Alternative splicing greatly increases the complexity of eukaryotic genomes, and provides a means for development- and tissue-specific gene expression. Dysregulation of alternative splicing may cause diseases. We particularly study how alternative splicing programs neuronal cell differentiation and impacts brain development. First, we have provided evidence indicating that the splicing factor RBM4 is involved in differentiation of muscle, pancreas and neuronal cells and radial migration of newborn neurons in the developing brain via its role in alternative splicing regulation. Second, we investigate several unprecedented roles of the post-splicing exon-junction complex. We recently found that one of its components (Y14) is involved in splicing regulation, mRNA cap binding, and genomic stability maintenance. At present, we explore the effect of Y14 deficiency on development using tissue-specific knockout. Third, we study the RNA helicase DDX3 in translational control in cancer and neuron. DDX3 promotes the translation of mRNAs whose 5' UTR has secondary structures or upstream open reading frames. These mRNAs encode oncogenic and migration related factors. Therefore, DDX3 contributes to cell cycle control and cell migration in cancer cells and modulates neurite and dendrite outgrowth as well as spin maturation in brain. Our studies provide the details for a wide range of RNA processing events and their regulation mechanisms.

研究介紹

神經及癌細胞之後轉錄基因調控

 

轉錄後調控對於真核細胞轉錄體 (transcriptome) 的表達有極為重要的影響。我們多年來一直在研究mRNA的代謝調控與細胞生理、分化和致病機轉的關係,我們近年在選擇性剪接及轉譯調控方面已有較具體的成果。選擇性剪接會大幅增加真核細胞轉錄體的複雜性,並可產生特定或具組織專一性的mRNA isoforms,基因多型性或突變以及剪接調控分子失控都可能改變剪接isoform表達的平衡,而使細胞失去正常功能。我們長期研究剪接調控分子RBM4參與的剪接反應和其生物功能,我們發現RBM4會影響發育基因的isoform表達,因而促進肌肉、胰島及神經細胞的分化,我們最近利用基因剔除小鼠發現RBM4會影響新生神經的移動,進而影響到對大腦皮質的發育。我們同時研究剪接後exon junction複合體蛋白Y14的功能,我們發現Y14可參與選擇性剪接的調控、影響基因體組的穩定性,甚至直接參與DNA修復,我們目前利用組織專一基因剔除小鼠模式,研究Y14缺失所造成的p53過量表達以及DNA損傷對發育的影響。由於RNA解螺旋酶DDX3的突變會引發癌症及神經失能,我們亦深入探討DDX3的生化及細胞功能,我們發現DDX3會幫助具有複雜結構的mRNA進行轉譯,並藉此影響細胞週期進行和細胞移動以及神經突觸的形成。我們抑制癌細胞內DDX3的表達便可順利降低腫瘤形成及癌轉移的機率。經由以上研究,我們對於轉錄後及轉譯調控和生理、發育的影響以及在醫學上的應用,已有更進一步認識。

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