UPF2 is a critical regulator of liver development, function and regeneration
| Autor: | Inge Damgaard, Bo T. Porse, Lina Thorén, Gitte A. Nørgaard, Anna M. Blom, Rehannah Borup, Frida C Bergstrom, Johannes Waage, Janus S. Jakobsen, Joachim Weischenfeldt, Hanne Cathrine Bisgaard |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Chromatin Immunoprecipitation
RNA Stability Science Regulator Biology Molecular Biology/RNA Splicing Gastroenterology and Hepatology/Hepatology Mice Gene expression Animals Immunoprecipitation Genetics Mice Knockout Developmental Biology/Organogenesis Messenger RNA Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Regeneration (biology) Gene Expression Profiling Alternative splicing Cell Cycle RNA-Binding Proteins Immunohistochemistry Liver regeneration Cell biology Gene expression profiling Liver Microscopy Fluorescence Molecular Biology/Post-Translational Regulation of Gene Expression Medicine Molecular Biology/mRNA Stability Carrier Proteins Chromatin immunoprecipitation Research Article |
| Zdroj: | PLoS ONE, Vol 5, Iss 7, p e11650 (2010) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | BackgroundNonsense-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 findingsHere 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/significanceCollectively, 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. |
| Databáze: | OpenAIRE |
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