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The Role of RNA Binding Proteins HnRNP A1 and HnRNP L in T Cells
The Role of RNA Binding Proteins HnRNP A1 and HnRNP L in T Cells
The Role of RNA Binding Proteins HnRNP A1 and HnRNP L in T Cells

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202105632
ISBN  
9798270217167
DDC  
611.4
저자명  
White, Tristan Lenora Augustus.
서명/저자  
The Role of RNA Binding Proteins HnRNP A1 and HnRNP L in T Cells
발행사항  
[Sl] : University of Pittsburgh, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
111 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-06, Section: B.
주기사항  
Advisor: Morel, Penelope;Kane, Lawrence P.;McGeachy, Mandy;D'Cruz, Louise;Atianand, Maninjay.
학위논문주기  
Thesis (Ph.D.)--University of Pittsburgh, 2024.
초록/해제  
요약While RNA binding proteins (RBPs) like heterogeneous nuclear ribonucleoproteins (hnRNPs) have recently emerged as regulators of gene expression in immune cells, their effect on T-cell fate needs further investigation. HnRNPs are crucial in many aspects of RNA biogenesis, alternative splicing, expression, and function. We and others have shown that TCR signaling strength through the PI3K/Akt/mTOR pathway can control T cell differentiation. Differences in PI3K/Akt/mTOR signaling affect T cell fate and potentially Akt phosphorylation of hnRNP A1, which depends on TCR signal strength. HnRNP A1 is known to have a single Akt phosphorylation site at S199, and our lab has generated a new mutant mouse model, hnRNP A1-S199A, to study the effect that phosphorylation of the hnRNP A1-S199 has on T cell fate and function. We found that the hnRNP A1-S199A mutation did not affect the immune system at steady state compared to the wild type. We also found no difference in Th1, Th2, Th17, and Treg differentiation in vitro. Using an in vivo oral tolerance model, we saw no difference in Treg induction or Tfh differentiation and function using an NP immunization model. During T cell development, hnRNP L is known to regulate the proliferation and migration of thymic pre-T cells, as loss of hnRNP L in early T cell development results in a failure of T cells to reach the periphery. Little is known about how hnRNP L affects T cell activation and function. Our lab has used CD4Cre x Hnrnplfl/fl (KO) mice model to understand the role of hnRNP L in peripheral T cells. We found that at steady state, KO CD4+ T cell mice have normal migration from the thymus, but there is a reduction in peripheral T cell percentage and numbers. We also show that hnRNP L plays an essential role in Th1, Th2, and Tregs differentiation and T cell survival in vitro. Using two in vivo NP immunization models, we pfound hnRNP L is critical for Tfh differentiation and germinal center formation. This study shows that hnRNP A1 S199 is not a primary site of phosphorylation, and hnRNP L expression is critical for T cell function and survival.
일반주제명  
Thymus gland
일반주제명  
Cytoplasm
일반주제명  
Signal transduction
일반주제명  
Pathogens
일반주제명  
Cell death
일반주제명  
Telomerase
일반주제명  
Phosphatase
일반주제명  
Disease
일반주제명  
Biosynthesis
일반주제명  
Cytokines
일반주제명  
Immunology
일반주제명  
RNA-protein interactions
일반주제명  
Immune response
일반주제명  
Lymphocytes
일반주제명  
Tumor necrosis factor-TNF
일반주제명  
Bone marrow
일반주제명  
Antigens
일반주제명  
Phosphorylation
일반주제명  
Viral infections
일반주제명  
Apoptosis
일반주제명  
Cell cycle
일반주제명  
Transcription factors
일반주제명  
Cellular biology
일반주제명  
Virology
기타저자  
University of Pittsburgh.
기본자료저록  
Dissertations Abstracts International. 87-06B.
전자적 위치 및 접속  
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MARC

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■035    ▼a(MiAaPQ)AAI32362945
■035    ▼a(MiAaPQ)Pittsburgh46350
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■0820  ▼a611.4
■1001  ▼aWhite,  Tristan  Lenora  Augustus.
■24510▼aThe  Role  of  RNA  Binding  Proteins  HnRNP  A1  and  HnRNP  L  in  T  Cells
■260    ▼a[Sl]▼bUniversity  of  Pittsburgh▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a111  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-06,  Section:  B.
■500    ▼aAdvisor:  Morel,  Penelope;Kane,  Lawrence  P.;McGeachy,  Mandy;D'Cruz,  Louise;Atianand,  Maninjay.
■5021  ▼aThesis  (Ph.D.)--University  of  Pittsburgh,  2024.
■520    ▼aWhile  RNA  binding  proteins  (RBPs)  like  heterogeneous  nuclear  ribonucleoproteins  (hnRNPs)  have  recently  emerged  as  regulators  of  gene  expression  in  immune  cells,  their  effect  on  T-cell  fate  needs  further  investigation.  HnRNPs  are  crucial  in  many  aspects  of  RNA  biogenesis,  alternative  splicing,  expression,  and  function.  We  and  others  have  shown  that  TCR  signaling  strength  through  the  PI3K/Akt/mTOR  pathway  can  control  T  cell  differentiation.  Differences  in  PI3K/Akt/mTOR  signaling  affect  T  cell  fate  and  potentially  Akt  phosphorylation  of  hnRNP  A1,  which  depends  on  TCR  signal  strength.  HnRNP  A1  is  known  to  have  a  single  Akt  phosphorylation  site  at  S199,  and  our  lab  has  generated  a  new  mutant  mouse  model,  hnRNP  A1-S199A,  to  study  the  effect  that  phosphorylation  of  the  hnRNP  A1-S199  has  on  T  cell  fate  and  function.  We  found  that  the  hnRNP  A1-S199A  mutation  did  not  affect  the  immune  system  at  steady  state  compared  to  the  wild  type.  We  also  found  no  difference  in  Th1,  Th2,  Th17,  and  Treg  differentiation  in  vitro.  Using  an  in  vivo  oral  tolerance  model,  we  saw  no  difference  in  Treg  induction  or  Tfh  differentiation  and  function  using  an  NP  immunization  model.  During  T  cell  development,  hnRNP  L  is  known  to  regulate  the  proliferation  and  migration  of  thymic  pre-T  cells,  as  loss  of  hnRNP  L  in  early  T  cell  development  results  in  a  failure  of  T  cells  to  reach  the  periphery.  Little  is  known  about  how  hnRNP  L  affects  T  cell  activation  and  function.  Our  lab  has  used  CD4Cre  x  Hnrnplfl/fl  (KO)  mice  model  to  understand  the  role  of  hnRNP  L  in  peripheral  T  cells.  We  found  that  at  steady  state,  KO  CD4+  T  cell  mice  have  normal  migration  from  the  thymus,  but  there  is  a  reduction  in  peripheral  T  cell  percentage  and  numbers.  We  also  show  that  hnRNP  L  plays  an  essential  role  in  Th1,  Th2,  and  Tregs  differentiation  and  T  cell  survival  in  vitro.  Using  two  in  vivo  NP  immunization  models,  we  pfound  hnRNP  L  is  critical  for  Tfh  differentiation  and  germinal  center  formation.  This  study  shows  that  hnRNP  A1  S199  is  not  a  primary  site  of  phosphorylation,  and  hnRNP  L  expression  is  critical  for  T  cell  function  and  survival.
■590    ▼aSchool  code:  0178.
■650  4▼aThymus  gland
■650  4▼aCytoplasm
■650  4▼aSignal  transduction
■650  4▼aPathogens
■650  4▼aCell  death
■650  4▼aTelomerase
■650  4▼aPhosphatase
■650  4▼aDisease
■650  4▼aBiosynthesis
■650  4▼aCytokines
■650  4▼aImmunology
■650  4▼aRNA-protein  interactions
■650  4▼aImmune  response
■650  4▼aLymphocytes
■650  4▼aTumor  necrosis  factor-TNF
■650  4▼aBone  marrow
■650  4▼aAntigens
■650  4▼aPhosphorylation
■650  4▼aViral  infections
■650  4▼aApoptosis
■650  4▼aCell  cycle
■650  4▼aTranscription  factors
■650  4▼aCellular  biology
■650  4▼aVirology
■690    ▼a0982
■690    ▼a0379
■690    ▼a0720
■71020▼aUniversity  of  Pittsburgh.
■7730  ▼tDissertations  Abstracts  International▼g87-06B.
■790    ▼a0178
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360878▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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