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 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.


RESULTS
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.


CONCLUSIONS
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.
Thoren
Lina A
LA
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Nørgaard
Gitte A
GA
Weischenfeldt
Joachim
J
Waage
Johannes
J
Jakobsen
Janus S
JS
Damgaard
Inge
I
Bergström
Frida C
FC
Blom
Anna M
AM
Borup
Rehannah
R
Bisgaard
Hanne Cathrine
HC
Porse
Bo T
BT
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D020871:RNA Stability / Q000235:genetics; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D016601:RNA-Binding Proteins; C529977:Upf2 protein, mouse