% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Hautke:1019431,
      author       = {Hautke, Alexander and Voronin, Arthur and Idiris, Fathia
                      and Riel, Anton and Lindner, Felix and Lelièvre-Büttner,
                      Amandine and Zhu, Jikang and Appel, Bettina and Fatti,
                      Edoardo and Weis, Karsten and Müller, Sabine and Schug,
                      Alexander and Ebbinghaus, Simon},
      title        = {{CAG}-{R}epeat {RNA} {H}airpin {F}olding and {R}ecruitment
                      to {N}uclear {S}peckles with a {P}ivotal {R}ole of {ATP} as
                      a {C}osolute},
      journal      = {Journal of the American Chemical Society},
      volume       = {145},
      number       = {17},
      issn         = {0002-7863},
      address      = {Washington, DC},
      publisher    = {ACS Publications},
      reportid     = {FZJ-2023-05388},
      pages        = {9571 - 9583},
      year         = {2023},
      abstract     = {A hallmark of Huntington’s disease (HD) is a prolonged
                      polyglutamine sequence in the huntingtin protein and,
                      correspondingly, an expanded cytosine, adenine, and guanine
                      (CAG) triplet repeat region in the mRNA. A majority of
                      studies investigating disease pathology were concerned with
                      toxic huntingtin protein, but the mRNA moved into focus due
                      to its recruitment to RNA foci and emerging novel
                      therapeutic approaches targeting the mRNA. A hallmark of
                      CAG-RNA is that it forms a stable hairpin in vitro which
                      seems to be crucial for specific protein interactions. Using
                      in-cell folding experiments, we show that the CAG-RNA is
                      largely destabilized in cells compared to dilute buffer
                      solutions but remains folded in the cytoplasm and nucleus.
                      Surprisingly, we found the same folding stability in the
                      nucleoplasm and in nuclear speckles under physiological
                      conditions suggesting that CAG-RNA does not undergo a
                      conformational transition upon recruitment to the nuclear
                      speckles. We found that the metabolite adenosine
                      triphosphate (ATP) plays a crucial role in promoting
                      unfolding, enabling its recruitment to nuclear speckles and
                      preserving its mobility. Using in vitro experiments and
                      molecular dynamics simulations, we found that the ATP
                      effects can be attributed to a direct interaction of ATP
                      with the nucleobases of the CAG-RNA rather than ATP acting
                      as “a fuel” for helicase activity. ATP-driven changes in
                      CAG-RNA homeostasis could be disease-relevant since
                      mitochondrial function is affected in HD disease progression
                      leading to a decline in cellular ATP levels.},
      cin          = {JSC},
      ddc          = {540},
      cid          = {I:(DE-Juel1)JSC-20090406},
      pnm          = {5111 - Domain-Specific Simulation $\&$ Data Life Cycle Labs
                      (SDLs) and Research Groups (POF4-511) / Cells In Silico -
                      Large Scale Tissue Simulations $(cellsinsilico_20200501)$ /
                      GRK 2450 - GRK 2450: Maßgeschneiderte Multiskalenmethoden
                      für Computersimulationen von nanoskaligen Materialien
                      (389000774) / HAF - Helmholtz Analytics Framework
                      (ZT-I-0003)},
      pid          = {G:(DE-HGF)POF4-5111 / $G:(DE-Juel1)cellsinsilico_20200501$
                      / G:(GEPRIS)389000774 / G:(DE-HGF)ZT-I-0003},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {37062072},
      UT           = {WOS:000974384000001},
      doi          = {10.1021/jacs.2c13653},
      url          = {https://juser.fz-juelich.de/record/1019431},
}