Y14調控RNA剪接之分子機制研究__臺灣博碩士論文知識加值系統

前驅傳訊核醣核酸（precursor message RNA, pre-mRNA）的剪接發生在轉錄時期，並受到trans-acting factors與cis-regulatory elements之交互調控。

資料載入處理中... 跳到主要內容 臺灣博碩士論文加值系統 ::: 網站導覽| 首頁| 關於本站| 聯絡我們| 國圖首頁| 常見問題| 操作說明 English |FB專頁 |Mobile 免費會員 登入| 註冊 功能切換導覽列 (188.166.176.73)您好！臺灣時間：2022/07/0315:54 字體大小：       ::: 詳目顯示 recordfocus 第1筆/ 共1筆  /1頁 論文基本資料 摘要 外文摘要 目次 參考文獻 紙本論文 QRCode 本論文永久網址: 複製永久網址Twitter研究生:林秉澤研究生(外文):Bin-TseLin論文名稱:Y14調控RNA剪接之分子機制研究論文名稱(外文):InvestigationtowardthemolecularmechanismunderlyingY14-mediatedsplicingregulation指導教授:譚婉玉指導教授(外文):Woan-YuhTarn口試委員:李芳仁、蔡欣祐口試委員(外文):Fang-JenLee、Hsin-YueTsai口試日期:2019-07-23學位類別:碩士校院名稱:國立臺灣大學系所名稱:分子醫學研究所學門:醫藥衛生學門學類:醫學學類論文種類:學術論文論文出版年:2019畢業學年度:107語文別:英文論文頁數:91中文關鍵詞:外顯子接合複合體、選擇性剪接、轉錄、小核核醣核酸U6、鹼基（腺苷）第六位的氮（N）甲基化修飾DOI:10.6342/NTU201902205相關次數: 被引用:0點閱:86評分:下載:0書目收藏:0 前驅傳訊核醣核酸（precursormessageRNA,pre-mRNA）的剪接發生在轉錄時期，並受到trans-actingfactors與cis-regulatoryelements之交互調控。

核醣核酸結合蛋白Y14是外顯子接合複合體（exonjunctioncomplex）之核心成員，但Y14本身可以影響pre-mRNA剪接。

我發現Y14的第166和168胺基酸位點的SA（serine-to-alanine）突變（Y14-SA）能修復因Y14缺失所造成的錯誤選擇性剪接（alternativesplicing）；我也發現RNA聚合酶或拓樸異構酶抑制劑有類似功能。

我亦觀察到正常和突變的Y14對基因的啟動子（promoter）有不同的親和性，因此Y14-SA是否透過轉錄機制來調控mRNA剪接仍需近一步調查。

另外，我們亦探討Y14是否藉由影響小核核醣核酸（snRNA）U6上第43個鹼基（腺苷）第六位的氮（N）元素上的甲基化修飾（N6-methyladenosine，m6A）來調控pre-mRNA剪接。

我們發現Y14跟核醣核酸去甲基酶ALKBH5和核醣核酸甲基酶METTL16結合，Y14在體外（invitro）會抑制ALKBH5的活性。

Y14表現量減少會使U6之m6A減少，但是藉由ALKBH5的大量表現或METTL16的表現減少所造成的U6之m6A減少，都不會產生選擇性剪接。

儘管如此，U6的m6A是否對pre-mRNA剪接有任何影響仍是不確定的。

我們仍持續研究Y14是否可藉由參與轉錄機制或U6的m6A來調控pre-mRNA之剪接。

Splicingoccursco-transcriptionallyandisregulatedbytrans-actingfactors(RNAbindingproteins)viabindingtocis-regulatoryRNAelements.Y14isacorefactoroftheexonjunctioncomplex(EJC),whichfunctionsinthepost-splicingevents,butrecentstudieshaverevealedthatdeletionofY14generatedaberrantalternativesplicingproducts.IunexpectedlydiscoveredthattheC-terminallytruncatedY14orphospho-deficientmutant(SA),butnotwildtypeY14,reversedY14knockdown-inducedsplicingchanges.Besides,inhibitionofRNApolymeraseIIandtopoisomeraseI&IIpreventedY14knockdown-inducedsplicingchangesonadifferentscale.Next,weevaluatedhowtheY14-SAmutantexertsthedominanteffect.Wehereobservedthatbothwild-typeandmutant(SA)Y14canbindthepromoterregionsofitstargetgenes,indicatingapotentialroleofY14incoordinatingtranscriptionandsplicing,whichisindependentofY14’sphosphorylation.Moreover,mycolleaguesandIfoundthatY14interactedwithboththeRNAdemethylaseALKBH5andRNAmethyltransferaseMETTL16.DepletionofY14reducedm6AmodificationonU6snRNA.However,depletionofMETTL16oroverexpressionofALKBH5,althoughminimallyaffectedm6AmodificationofU6snRNA,hadnoeffectonalternativesplicingofY14targetgenes.Atpresent,whetherm6AmodificationofU6snRNAisessentialforsplicingorinvolvedinsplicingregulationisyetunclear.Besides,wefoundthatY14inhibitedthedemethylaseactivityofALKBH5invitro.WhethertheinteractionbetweenY14andm6Amodifyingenzymeshasanybiologicalfunctionsremainstobeexamined.InvestigationofY14’sroleinsplicingregulationisstillongoing. ContentsIListofFigures/AppendixesIIAcknowledgementsIIIChineseAbstractIVEnglishAbstractVIntroduction1.Thesplicingmachinery12.Roleoftheexonjunctioncomplex(EJC6)inmRNAmetabolism43.RoleoftheEJCanditsperipheralfactorsinpre-mRNAsplicing64.Impactspromoterproximalpausing85.RoleofN6-methyladenosinemodificationinsplicing10Results1.Non-phosphorylatedY14restoressplicingchangescausedbyY14depletion152.Y14maycoordinatewiththetranscriptionmachineryinsplicingregulation173.Weak5’splicesiteaccountsforY14loss-inducedintronretention184.Y14-mediatedm6AmodificationofU6snRNAisnotcriticalforsplicingregulation195.Y14interactswithm6Amodifyingenzymes226.Y14inhibitsthedemethylationactivityofALKBH5invitro247.Novelm6A-containingsmallRNAs25Discussion27ExperimentalProcedures37References52Figures76Appendixes89 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 國圖紙本論文 推文 網路書籤 推薦 評分 引用網址 轉寄                                                                                                                                                                                                                    top 相關論文 相關期刊 熱門點閱論文 無相關論文   無相關期刊   1. 產業朝循環經濟商業模式轉型對我國資源利用及經濟之效益評估－以共享汽車為例 2. 丙胺酸重複片段對蛋白質在細胞核內分佈之影響 3. 平台經濟工作者之勞動關係認定基準-以英國Uber最高法院判決為例 4. 基於雲霧端架構之人工智慧服務延遲敏感任務卸載機制 5. 基於像散式光學輪廓儀之定量反射率量測方法 6. 動態均衡的無政府狀態價格 7. 基於SOT-MRAM之記憶體內卷積神經網路運算架構 8. 食物外送平台是否應該強制商家統一內外用價格？ 9. 人生最後一哩由他陪伴，送行者的專業化之路 10. 以貝氏方法最佳化控制高階諧波產生超短阿秒雷射 11. 界面工程與配位化學應用於有機無機混成鈣鈦礦太陽能電池之研究 12. 華人文化中之脈絡性普遍主義：情境故事法分析取向 13. 在財務艱困公司案件中會計師如何扮演企業醫師之探討—以M國際購物中心個案為例 14. 從告身到法書：徐浩〈朱巨川告身〉卷研究     簡易查詢 | 進階查詢 | 熱門排行 | 我的研究室