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A Ubiquitous GC Content Signature Underlies Multimodal mRNA Regulation by DDX3X
A Ubiquitous GC Content Signature Underlies Multimodal mRNA Regulation by DDX3X
A Ubiquitous GC Content Signature Underlies Multimodal mRNA Regulation by DDX3X

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211151120
ISBN  
9798382816104
DDC  
574
저자명  
Jowhar, Ziad Mohamoud.
서명/저자  
A Ubiquitous GC Content Signature Underlies Multimodal mRNA Regulation by DDX3X
발행사항  
[Sl] : University of California, San Francisco, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
83 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
주기사항  
Includes supplementary digital materials.
주기사항  
Advisor: Weiss, William.
학위논문주기  
Thesis (Ph.D.)--University of California, San Francisco, 2024.
초록/해제  
요약DDX3X encodes for a DEAD-box RNA helicase that promotes the translation of mRNAs that contain long, highly structured 5' UTRs. DDX3X interacts with translation initiation factors and can remodel mRNA structures or RNA protein complexes in an ATP-dependent manner. Our prior work found that DDX3X depletion leads to changes in translation and RNA levels while missense variants selectively impact translation, implicating DDX3X in regulating mRNA stability. Despite being an essential gene and implicated in several human cancers and developmental diseases, including intellectual disability and autism spectrum disorder, the mechanisms of DDX3X in post-transcriptional gene regulation and mRNA metabolism remain poorly understood. To address this gap in knowledge in DDX3X function in post-transcriptional gene regulation and mRNA metabolism, this work studied the mechanism of how DDX3X regulates specific mRNA transcripts and confers stability or loss of stability and how this process is altered with loss of DDX3X. DDX3X's function in translation is well characterized, is known to be involved in nuclear export of specific mRNA, and our preliminary data demonstrates that DDX3X specific transcripts have altered stability. However, what features and characteristics of these DDX3X-dependent transcripts are key for DDX3X driven stability remain unknown. This study aimed to define what features of mRNA transcripts are key for how DDX3X regulates RNA metabolism both at the level of translation and transcript stability. This knowledge is critical for advancing our knowledge in post-transcriptional gene regulation and mRNA metabolism.
일반주제명  
Molecular biology
일반주제명  
Bioinformatics
일반주제명  
Cellular biology
일반주제명  
Genetics
키워드  
Post-transcriptional gene regulation
키워드  
Intellectual disability
키워드  
mRNA metabolism
키워드  
Translation
기타저자  
University of California, San Francisco Biomedical Sciences
기본자료저록  
Dissertations Abstracts International. 85-12B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aJowhar,  Ziad  Mohamoud.▼0(orcid)0000-0002-3536-079
■24512▼aA  Ubiquitous  GC  Content  Signature  Underlies  Multimodal  mRNA Regulation  by  DDX3X
■260    ▼a[Sl]▼bUniversity  of  California,  San  Francisco▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a83  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-12,  Section:  B.
■500    ▼aIncludes  supplementary  digital  materials.
■500    ▼aAdvisor:  Weiss,  William.
■5021  ▼aThesis  (Ph.D.)--University  of  California,  San  Francisco,  2024.
■520    ▼aDDX3X  encodes  for  a  DEAD-box  RNA  helicase  that  promotes  the  translation  of  mRNAs  that  contain  long,  highly  structured  5'  UTRs.  DDX3X  interacts  with  translation  initiation  factors  and  can  remodel  mRNA  structures  or  RNA  protein  complexes  in  an  ATP-dependent  manner.  Our  prior  work  found  that  DDX3X  depletion  leads  to  changes  in  translation  and  RNA  levels  while  missense  variants  selectively  impact  translation,  implicating  DDX3X  in  regulating  mRNA  stability.  Despite  being  an  essential  gene  and  implicated  in  several  human  cancers  and  developmental  diseases,  including  intellectual  disability  and  autism  spectrum  disorder,  the  mechanisms  of  DDX3X  in  post-transcriptional  gene  regulation  and  mRNA  metabolism  remain  poorly  understood. To  address  this  gap  in  knowledge  in  DDX3X  function  in  post-transcriptional  gene  regulation  and  mRNA  metabolism,  this  work  studied  the  mechanism  of  how  DDX3X  regulates  specific  mRNA  transcripts  and  confers  stability  or  loss  of  stability  and  how  this  process  is  altered  with  loss  of  DDX3X.  DDX3X's  function  in  translation  is  well  characterized,  is  known  to  be  involved  in  nuclear  export  of  specific  mRNA,  and  our  preliminary  data  demonstrates  that  DDX3X  specific  transcripts  have  altered  stability.  However,  what  features  and  characteristics  of  these  DDX3X-dependent  transcripts  are  key  for  DDX3X  driven  stability  remain  unknown.  This  study  aimed  to  define  what  features  of  mRNA  transcripts  are  key  for  how  DDX3X  regulates  RNA  metabolism  both  at  the  level  of  translation  and  transcript  stability.  This  knowledge  is  critical  for  advancing  our  knowledge  in  post-transcriptional  gene  regulation  and  mRNA  metabolism.
■590    ▼aSchool  code:  0034.
■650  4▼aMolecular  biology
■650  4▼aBioinformatics
■650  4▼aCellular  biology
■650  4▼aGenetics
■653    ▼aPost-transcriptional  gene  regulation
■653    ▼aIntellectual  disability
■653    ▼amRNA  metabolism
■653    ▼aTranslation
■690    ▼a0307
■690    ▼a0715
■690    ▼a0379
■690    ▼a0369
■71020▼aUniversity  of  California,  San  Francisco▼bBiomedical  Sciences.
■7730  ▼tDissertations  Abstracts  International▼g85-12B.
■790    ▼a0034
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160806▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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