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Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts

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  • Nicola Meola
  • ,
  • Michal Domanski
  • ,
  • Evdoxia Karadoulama
  • Yun Chen, The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloesvej 5, DK-2200 Copenhagen, Denmark.
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  • Coline Gentil, Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, Building 1130, DK-8000 Aarhus C, Denmark.
  • ,
  • Dennis Pultz, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M (Denmark).
  • ,
  • Kristoffer Vitting-Seerup, The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloesvej 5, DK-2200 Copenhagen, Denmark.
  • ,
  • Søren Lykke-Andersen
  • Jens S Andersen, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M (Denmark).
  • ,
  • Albin Sandelin, The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloesvej 5, DK-2200 Copenhagen, Denmark.
  • ,
  • Torben Heick Jensen

The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its co-factor Mtr4p/hMTR4, which links to RNA-binding protein adaptors. One example is the trimeric human nuclear exosome targeting (NEXT) complex, which is composed of hMTR4, the Zn-finger protein ZCCHC8, and the RNA-binding factor RBM7. NEXT primarily targets early and unprocessed transcripts, which demands a rationale for how the nuclear exosome recognizes processed RNAs. Here, we describe the poly(A) tail exosome targeting (PAXT) connection, which comprises the ZFC3H1 Zn-knuckle protein as a central link between hMTR4 and the nuclear poly(A)-binding protein PABPN1. Individual depletion of ZFC3H1 and PABPN1 results in the accumulation of common transcripts that are generally both longer and more extensively polyadenylated than NEXT substrates. Importantly, ZFC3H1/PABPN1 and ZCCHC8/RBM7 contact hMTR4 in a mutually exclusive manner, revealing that the exosome targets nuclear transcripts of different maturation status by substituting its hMTR4-associating adaptors.

Original languageEnglish
JournalMolecular Cell
Volume64
Issue3
Pages (from-to)520-533
Number of pages14
ISSN1097-2765
DOIs
Publication statusPublished - 3 Nov 2016

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