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Toward a Deeper Understanding and Appreciation of Stress-Induced Biomolecular Condensation
Toward a Deeper Understanding and Appreciation of Stress-Induced Biomolecular Condensation
Toward a Deeper Understanding and Appreciation of Stress-Induced Biomolecular Condensation

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211152815
ISBN  
9798384081432
DDC  
574
저자명  
Wong Hickernell, Caitlin Joy.
서명/저자  
Toward a Deeper Understanding and Appreciation of Stress-Induced Biomolecular Condensation
발행사항  
[Sl] : The University of Chicago, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
189 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
주기사항  
Advisor: Drummond, David A.
학위논문주기  
Thesis (Ph.D.)--The University of Chicago, 2024.
초록/해제  
요약When cells experience stress, they undergo a number of dramatic intracellular molecular changes. One of these changes is the formation of biomolecular condensates, or clusters of mRNA and proteins. When these clusters are visible by microscopy, they are called "stress granules." Although these condensates have been observed for many years across many species, many questions remain. What exactly is the composition of a stress granule? What is the mechanism of formation? What, if any, is the function of stress granules? Are they an adaptive response by the cell? The field has not coalesced around answers to these fundamental questions, compelling further study.This dissertation covers a review of stress granules, summarizing previous work and outlining the grand challenges in this area. Additionally, it includes a project on the stress-induced condensation of mRNA. During stress in yeast, we observed global, length-independent condensation of mRNA that seems to be regulated by a block in translation initiation. We also observed that stress-induced transcripts are excluded from condensates, driven by the timing of transcription. Finally, our data suggest the existence of small, submicroscopic condensates that are not visible by standard microscopy. We propose a model where stress-induced mRNA condensation allows the cell to prioritize translation during stress, sequestering away old transcripts so the cell can focus on a stress-specific translational program. Lastly, this work includes a study on whether the stress-induced condensation behavior of poly-A binding protein 1 (Pab1) regulates the translation of stress transcripts during recovery from stress. We did not find data to support this model, leaving Pab1's adaptive condensation behavior as an open question.As a whole, this work comments broadly on stress granules and specifically on how condensation does and does not contribute to the stress response in yeast. It also points toward future challenges and goals, such as a deeper understanding of the mechanism of mRNA condensation and its precise adaptive role during stress.
일반주제명  
Biochemistry
일반주제명  
Cellular biology
일반주제명  
Molecular biology
키워드  
Biomolecular condensation
키워드  
Heat shock
키워드  
Stress granule
키워드  
Yeast
기타저자  
The University of Chicago Biochemistry and Molecular Biophysics
기본자료저록  
Dissertations Abstracts International. 86-03B.
전자적 위치 및 접속  
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MARC

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■035    ▼a(MiAaPQ)AAI31558664
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a574
■1001  ▼aWong  Hickernell,  Caitlin  Joy.▼0(orcid)0000-0001-8066-3186
■24510▼aToward  a  Deeper  Understanding  and  Appreciation  of  Stress-Induced  Biomolecular  Condensation
■260    ▼a[Sl]▼bThe  University  of  Chicago▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a189  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-03,  Section:  B.
■500    ▼aAdvisor:  Drummond,  David  A.
■5021  ▼aThesis  (Ph.D.)--The  University  of  Chicago,  2024.
■520    ▼aWhen  cells  experience  stress,  they  undergo  a  number  of  dramatic  intracellular  molecular  changes.  One  of  these  changes  is  the  formation  of  biomolecular  condensates,  or  clusters  of  mRNA  and  proteins.  When  these  clusters  are  visible  by  microscopy,  they  are  called  "stress  granules."  Although  these  condensates  have  been  observed  for  many  years  across  many  species,  many  questions  remain.  What  exactly  is  the  composition  of  a  stress  granule?  What  is  the  mechanism  of  formation?  What,  if  any,  is  the  function  of  stress  granules?  Are  they  an  adaptive  response  by  the  cell?  The  field  has  not  coalesced  around  answers  to  these  fundamental  questions,  compelling  further  study.This  dissertation  covers  a  review  of  stress  granules,  summarizing  previous  work  and  outlining  the  grand  challenges  in  this  area.  Additionally,  it  includes  a  project  on  the  stress-induced  condensation  of  mRNA.  During  stress  in  yeast,  we  observed  global,  length-independent  condensation  of  mRNA  that  seems  to  be  regulated  by  a  block  in  translation  initiation.  We  also  observed  that  stress-induced  transcripts  are  excluded  from  condensates,  driven  by  the  timing  of  transcription.  Finally,  our  data  suggest  the  existence  of  small,  submicroscopic  condensates  that  are  not  visible  by  standard  microscopy.  We  propose  a  model  where  stress-induced  mRNA  condensation  allows  the  cell  to  prioritize  translation  during  stress,  sequestering  away  old  transcripts  so  the  cell  can  focus  on  a  stress-specific  translational  program.  Lastly,  this  work  includes  a  study  on  whether  the  stress-induced  condensation  behavior  of  poly-A  binding  protein  1  (Pab1)  regulates  the  translation  of  stress  transcripts  during  recovery  from  stress.  We  did  not  find  data  to  support  this  model,  leaving  Pab1's  adaptive  condensation  behavior  as  an  open  question.As  a  whole,  this  work  comments  broadly  on  stress  granules  and  specifically  on  how  condensation  does  and  does  not  contribute  to  the  stress  response  in  yeast.  It  also  points  toward  future  challenges  and  goals,  such  as  a  deeper  understanding  of  the  mechanism  of  mRNA  condensation  and  its  precise  adaptive  role  during  stress.
■590    ▼aSchool  code:  0330.
■650  4▼aBiochemistry
■650  4▼aCellular  biology
■650  4▼aMolecular  biology
■653    ▼aBiomolecular  condensation
■653    ▼aHeat  shock
■653    ▼aStress  granule
■653    ▼aYeast
■690    ▼a0487
■690    ▼a0379
■690    ▼a0307
■71020▼aThe  University  of  Chicago▼bBiochemistry  and  Molecular  Biophysics.
■7730  ▼tDissertations  Abstracts  International▼g86-03B.
■790    ▼a0330
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17163970▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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