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UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration

BACKGROUND: Nonsense-mediated mRNA decay (NMD) is a post-transcriptional RNA surveillance process that facilitates the recognition and destruction of mRNAs bearing premature terminations codons (PTCs). Such PTC-containing (PTC+) mRNAs may arise from different processes, including erroneous processin...

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Autores principales: Thoren, Lina A., Nørgaard, Gitte A., Weischenfeldt, Joachim, Waage, Johannes, Jakobsen, Janus S., Damgaard, Inge, Bergström, Frida C., Blom, Anna M., Borup, Rehannah, Bisgaard, Hanne Cathrine, Porse, Bo T.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906512/
https://www.ncbi.nlm.nih.gov/pubmed/20657840
http://dx.doi.org/10.1371/journal.pone.0011650
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author Thoren, Lina A.
Nørgaard, Gitte A.
Weischenfeldt, Joachim
Waage, Johannes
Jakobsen, Janus S.
Damgaard, Inge
Bergström, Frida C.
Blom, Anna M.
Borup, Rehannah
Bisgaard, Hanne Cathrine
Porse, Bo T.
author_facet Thoren, Lina A.
Nørgaard, Gitte A.
Weischenfeldt, Joachim
Waage, Johannes
Jakobsen, Janus S.
Damgaard, Inge
Bergström, Frida C.
Blom, Anna M.
Borup, Rehannah
Bisgaard, Hanne Cathrine
Porse, Bo T.
author_sort Thoren, Lina A.
collection PubMed
description BACKGROUND: Nonsense-mediated mRNA decay (NMD) is a post-transcriptional RNA surveillance process that facilitates the recognition and destruction of mRNAs bearing premature terminations codons (PTCs). Such PTC-containing (PTC+) mRNAs may arise from different processes, including erroneous processing and expression of pseudogenes, but also from more regulated events such as alternative splicing coupled NMD (AS-NMD). Thus, the NMD pathway serves both as a silencer of genomic noise and a regulator of gene expression. Given the early embryonic lethality in NMD deficient mice, uncovering the full regulatory potential of the NMD pathway in mammals will require the functional assessment of NMD in different tissues. METHODOLOGY/PRINCIPAL FINDINGS: Here we use mouse genetics to address the role of UPF2, a core NMD component, in the development, function and regeneration of the liver. We find that loss of NMD during fetal liver development is incompatible with postnatal life due to failure of terminal differentiation. Moreover, deletion of Upf2 in the adult liver results in hepatosteatosis and disruption of liver homeostasis. Finally, NMD was found to be absolutely required for liver regeneration. CONCLUSION/SIGNIFICANCE: Collectively, our data demonstrate the critical role of the NMD pathway in liver development, function and regeneration and highlights the importance of NMD for mammalian biology.
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spelling pubmed-29065122010-07-23 UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration Thoren, Lina A. Nørgaard, Gitte A. Weischenfeldt, Joachim Waage, Johannes Jakobsen, Janus S. Damgaard, Inge Bergström, Frida C. Blom, Anna M. Borup, Rehannah Bisgaard, Hanne Cathrine Porse, Bo T. PLoS One Research Article BACKGROUND: Nonsense-mediated mRNA decay (NMD) is a post-transcriptional RNA surveillance process that facilitates the recognition and destruction of mRNAs bearing premature terminations codons (PTCs). Such PTC-containing (PTC+) mRNAs may arise from different processes, including erroneous processing and expression of pseudogenes, but also from more regulated events such as alternative splicing coupled NMD (AS-NMD). Thus, the NMD pathway serves both as a silencer of genomic noise and a regulator of gene expression. Given the early embryonic lethality in NMD deficient mice, uncovering the full regulatory potential of the NMD pathway in mammals will require the functional assessment of NMD in different tissues. METHODOLOGY/PRINCIPAL FINDINGS: Here we use mouse genetics to address the role of UPF2, a core NMD component, in the development, function and regeneration of the liver. We find that loss of NMD during fetal liver development is incompatible with postnatal life due to failure of terminal differentiation. Moreover, deletion of Upf2 in the adult liver results in hepatosteatosis and disruption of liver homeostasis. Finally, NMD was found to be absolutely required for liver regeneration. CONCLUSION/SIGNIFICANCE: Collectively, our data demonstrate the critical role of the NMD pathway in liver development, function and regeneration and highlights the importance of NMD for mammalian biology. Public Library of Science 2010-07-19 /pmc/articles/PMC2906512/ /pubmed/20657840 http://dx.doi.org/10.1371/journal.pone.0011650 Text en Thoren et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Thoren, Lina A.
Nørgaard, Gitte A.
Weischenfeldt, Joachim
Waage, Johannes
Jakobsen, Janus S.
Damgaard, Inge
Bergström, Frida C.
Blom, Anna M.
Borup, Rehannah
Bisgaard, Hanne Cathrine
Porse, Bo T.
UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration
title UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration
title_full UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration
title_fullStr UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration
title_full_unstemmed UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration
title_short UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration
title_sort upf2 is a critical regulator of liver development, function and regeneration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906512/
https://www.ncbi.nlm.nih.gov/pubmed/20657840
http://dx.doi.org/10.1371/journal.pone.0011650
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