upf2 is a critical regulator of liver development, function and regenerationupf2肝脏发展是一个至关重要的监管机构,功能和再生.pdfVIP

UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration Lina A. Thoren1,2., Gitte A. Nørgaard1,2., Joachim Weischenfeldt1,2., Johannes Waage1,2, Janus S. 1,2,3 1,2 ¨ 4 4 5 Jakobsen , Inge Damgaard , Frida C. Bergstrom , Anna M. Blom , Rehannah Borup , Hanne Cathrine Bisgaard6, Bo T. Porse1,2* 1 Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark, 2 Section for Gene Therapy Research, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark, 3 Finsen Laboratory, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark, 4 Department of Laboratory Medicine, ¨ ¨ Lund University, Malmo University Hospital, Malmo, Sweden, 5 Department of Clinical Biochemistry, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark, 6 Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark Abstract 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 ro